Pub Date : 2024-10-31DOI: 10.1016/j.atherosclerosis.2024.119042
Chieh-Li Yen , Pei-Chun Fan , Cheng-Chia Lee , Jia-Jin Chen , Chao-Yu Chen , Yi-Ran Tu , Pao-Hsien Chu , Ching-Chung Hsiao , Yung-Chang Chen , Chih-Hsiang Chang
Background and aims
Different from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients.
Methods
By using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics.
Results
At 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes.
Conclusions
Maintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.
背景和目的：与其他心血管（CV）高风险人群不同，支持慢性肾脏病（CKD）患者使用他汀类药物降低低密度脂蛋白胆固醇（LDL-C）对CV具有保护作用的证据相对较少。本研究旨在探讨维持较低 LDL-C 水平在晚期 CKD 患者中的作用：方法：利用长庚研究数据库，以台湾最大的医疗集团为基础，提取了5367名新诊断为CKD第4阶段并接受他汀类药物治疗的成年患者，并根据他们的LDL-C水平进一步分为三组：结果：在5年的随访中，LDL-C < 70 mg/dL组的澳门巴黎人娱乐官网风险（14.3 % vs. 18.7 %，危险比[HR]：0.77，95 % CI：0.69-0.86）、心血管死亡风险（7.1 % vs. 9.7 %，亚分布HR [SHR]：0.75，95 % CI：0.65-0.88）、缺血性中风（4.1% vs. 5.4%，[SHR]：0.65，95 % CI：0.54-0.79）和需要慢性透析的新发终末期肾病（25.6% vs. 29.4%，SHR：0.87，95 % CI：0.80-0.91）。相比之下，低密度脂蛋白胆固醇水平介于70和100之间的组别与低密度脂蛋白胆固醇>100毫克/分升的组别在研究结果上没有显著差异：结论：维持低密度脂蛋白胆固醇低于 70 毫克/分升可能有利于晚期 CKD 患者的心血管保护，随着 CKD 的进展，可能需要更低的低密度脂蛋白胆固醇治疗目标。
{"title":"The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients","authors":"Chieh-Li Yen , Pei-Chun Fan , Cheng-Chia Lee , Jia-Jin Chen , Chao-Yu Chen , Yi-Ran Tu , Pao-Hsien Chu , Ching-Chung Hsiao , Yung-Chang Chen , Chih-Hsiang Chang","doi":"10.1016/j.atherosclerosis.2024.119042","DOIUrl":"10.1016/j.atherosclerosis.2024.119042","url":null,"abstract":"<div><h3>Background and aims</h3><div>Different from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients.</div></div><div><h3>Methods</h3><div>By using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics.</div></div><div><h3>Results</h3><div>At 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes.</div></div><div><h3>Conclusions</h3><div>Maintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 119042"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1016/j.atherosclerosis.2024.118586
Ziyi Guo , Yuze Zhang , Zekun Peng , Haojie Rao , Jianfeng Yang , Zengrong Chen , Wenchao Song , Qing Wan , Hong Chen , Miao Wang
Background and aims
Vascular restenosis due to neointima hyperplasia limits the long-term patency of stented arteries, resulting in angioplasty failure. The complement system has been implicated in restenosis. This study aimed to investigate the role of complement factor B (fB), an essential component of the alternative pathway of complement activation, in neointima formation.
Methods
Angioplasty wire injury was conducted using 12-week-old mice deficient in fB or C9 (the main component of the membrane attacking complex, C5b-9) and littermate controls and neointima formation were assessed. Vascular smooth muscle cell (SMC) and endothelial cell (EC) proliferation and migration were examined in vitro.
Results
fB was mainly detected in SMCs of stenotic arteries from humans and mice. Deletion of fB substantially reduced the neointima area and intima-to-media area ratio without affecting the media area at 28 days after injury. At 7 days after injury, fB deficiency decreased SMC proliferation, unaltering neointimal macrophage infiltration and EC reendothelialization. Vascular SMC-expressed fB, not the circulation-sourced fB, played an essential role in SMC proliferation and migration in vitro. fB deficient mice exhibited lower levels of the soluble form of C5b-9, however, deletion of C9 did not alter neointima formation after wire injury, consistent with the null impact of C9 deficiency on SMC proliferation in vitro.
Conclusions
fB promotes neointima formation following wire-induced artery injury independent of forming the membrane-attacking complex. This is attributable to fB-dependent SMC proliferation and migration without affecting EC function. Targeting fB might protect against restenosis after percutaneous coronary intervention.
{"title":"Complement factor B, not the membrane attack complex component C9, promotes neointima formation after arterial wire injury","authors":"Ziyi Guo , Yuze Zhang , Zekun Peng , Haojie Rao , Jianfeng Yang , Zengrong Chen , Wenchao Song , Qing Wan , Hong Chen , Miao Wang","doi":"10.1016/j.atherosclerosis.2024.118586","DOIUrl":"10.1016/j.atherosclerosis.2024.118586","url":null,"abstract":"<div><h3>Background and aims</h3><div>Vascular restenosis due to neointima hyperplasia limits the long-term patency of stented arteries, resulting in angioplasty failure. The complement system has been implicated in restenosis. This study aimed to investigate the role of complement factor B (fB), an essential component of the alternative pathway of complement activation, in neointima formation.</div></div><div><h3>Methods</h3><div>Angioplasty wire injury was conducted using 12-week-old mice deficient in fB or C9 (the main component of the membrane attacking complex, C5b-9) and littermate controls and neointima formation were assessed. Vascular smooth muscle cell (SMC) and endothelial cell (EC) proliferation and migration were examined <em>in vitro</em>.</div></div><div><h3>Results</h3><div>fB was mainly detected in SMCs of stenotic arteries from humans and mice. Deletion of fB substantially reduced the neointima area and intima-to-media area ratio without affecting the media area at 28 days after injury. At 7 days after injury, fB deficiency decreased SMC proliferation, unaltering neointimal macrophage infiltration and EC reendothelialization. Vascular SMC-expressed fB, not the circulation-sourced fB, played an essential role in SMC proliferation and migration <em>in vitro</em>. fB deficient mice exhibited lower levels of the soluble form of C5b-9, however, deletion of C9 did not alter neointima formation after wire injury, consistent with the null impact of C9 deficiency on SMC proliferation <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>fB promotes neointima formation following wire-induced artery injury independent of forming the membrane-attacking complex. This is attributable to fB-dependent SMC proliferation and migration without affecting EC function. Targeting fB might protect against restenosis after percutaneous coronary intervention.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118586"},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-19DOI: 10.1016/j.atherosclerosis.2024.118630
A Benitez-Amaro, E Garcia, M T La Chica Lhoëst, A Martínez, C Borràs, M Tondo, M V Céspedes, P Caruana, A Pepe, B Bochicchio, A Cenarro, F Civeira, R Prades, J C Escola-Gil, V Llorente-Cortés
Background and aims: Low-density lipoprotein (LDL) aggregation is nowadays considered a therapeutic target in atherosclerosis. DP3, the retro-enantio version of the sequence Gly1127-Cys1140 of LRP1, efficiently inhibits LDL aggregation and foam cell in vitro formation. Here, we investigate whether DP3 modulates atherosclerosis in a humanized ApoB100, LDL receptor (LDLR) knockout mice (Ldlr-/-hApoB100 Tg) and determine the potential LDL-related underlying mechanisms.
Methods: Tg mice were fed an HFD for 21 days to induce atherosclerosis and then randomized into three groups that received a daily subcutaneous administration (10 mg/kg) of i) vehicle, ii) DP3 peptide, or iii) a non-active peptide (IP321). The in vivo biodistribution of a fluorescent-labeled peptide version (TAMRA-DP3), and its colocalization with ApoB100 in the arterial intima, was analyzed by imaging system (IVIS) and confocal microscopy. Heart aortic roots were used for atherosclerosis detection and quantification. LDL functionality was analyzed by biochemical, biophysical, molecular, and cellular studies.
Results: Intimal neutral lipid accumulation in the aortic root was reduced in the DP3-treated group as compared to control groups. ApoB100 in LDLs from the DP3 group exhibited an increased percentage of α-helix secondary structures and decreased immunoreactivity to anti-ApoB100 antibodies. LDL from DP3-treated mice were protected against passive and sphingomyelinase (SMase)-induced aggregation, although they still experienced SMase-induced sphingomyelin phospholysis. In patients with familial hypercholesterolemia (FH), DP3 efficiently inhibited both SMase-induced phospholysis and aggregation.
Conclusions: DP3 peptide administration inhibits atherosclerosis by preserving the α-helix secondary structures of ApoB100 in a humanized ApoB100 murine model that mimicks the hallmark of human hypercholesterolemia.
{"title":"Targeting LDL aggregation decreases atherosclerotic lipid burden in a humanized mouse model of familial hypercholesterolemia: Crucial role of ApoB100 conformational stabilization.","authors":"A Benitez-Amaro, E Garcia, M T La Chica Lhoëst, A Martínez, C Borràs, M Tondo, M V Céspedes, P Caruana, A Pepe, B Bochicchio, A Cenarro, F Civeira, R Prades, J C Escola-Gil, V Llorente-Cortés","doi":"10.1016/j.atherosclerosis.2024.118630","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118630","url":null,"abstract":"<p><strong>Background and aims: </strong>Low-density lipoprotein (LDL) aggregation is nowadays considered a therapeutic target in atherosclerosis. DP3, the retro-enantio version of the sequence Gly<sup>1127</sup>-Cys<sup>1140</sup> of LRP1, efficiently inhibits LDL aggregation and foam cell in vitro formation. Here, we investigate whether DP3 modulates atherosclerosis in a humanized ApoB100, LDL receptor (LDLR) knockout mice (Ldlr<sup>-/-</sup>hApoB100 Tg) and determine the potential LDL-related underlying mechanisms.</p><p><strong>Methods: </strong>Tg mice were fed an HFD for 21 days to induce atherosclerosis and then randomized into three groups that received a daily subcutaneous administration (10 mg/kg) of i) vehicle, ii) DP3 peptide, or iii) a non-active peptide (IP321). The in vivo biodistribution of a fluorescent-labeled peptide version (TAMRA-DP3), and its colocalization with ApoB100 in the arterial intima, was analyzed by imaging system (IVIS) and confocal microscopy. Heart aortic roots were used for atherosclerosis detection and quantification. LDL functionality was analyzed by biochemical, biophysical, molecular, and cellular studies.</p><p><strong>Results: </strong>Intimal neutral lipid accumulation in the aortic root was reduced in the DP3-treated group as compared to control groups. ApoB100 in LDLs from the DP3 group exhibited an increased percentage of α-helix secondary structures and decreased immunoreactivity to anti-ApoB100 antibodies. LDL from DP3-treated mice were protected against passive and sphingomyelinase (SMase)-induced aggregation, although they still experienced SMase-induced sphingomyelin phospholysis. In patients with familial hypercholesterolemia (FH), DP3 efficiently inhibited both SMase-induced phospholysis and aggregation.</p><p><strong>Conclusions: </strong>DP3 peptide administration inhibits atherosclerosis by preserving the α-helix secondary structures of ApoB100 in a humanized ApoB100 murine model that mimicks the hallmark of human hypercholesterolemia.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"118630"},"PeriodicalIF":4.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.atherosclerosis.2024.118635
Ankia Visser , Willemien van Zwol , Niels Kloosterhuis , Nicolette Huijkman , Marieke Smit , Mirjam Koster , Vincent Bloks , M. Mahmood Hussain , Bart van de Sluis , Jan Albert Kuivenhoven
Background and aims
The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood.
Methods and Results
Using human transcriptome datasets to find genes co-regulated with MTTP, we identified ERICH4 as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between ERICH4 and plasma lipids. To validate ERICH4 as a lipid gene, we generated whole-body Erich4 knockout (Erich4−/−) mice. ERICH4 deficiency, however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either.
Conclusions
Despite prediction tools indicating ERICH4 as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.
{"title":"ERICH4 is not involved in the assembly and secretion of intestinal lipoproteins","authors":"Ankia Visser , Willemien van Zwol , Niels Kloosterhuis , Nicolette Huijkman , Marieke Smit , Mirjam Koster , Vincent Bloks , M. Mahmood Hussain , Bart van de Sluis , Jan Albert Kuivenhoven","doi":"10.1016/j.atherosclerosis.2024.118635","DOIUrl":"10.1016/j.atherosclerosis.2024.118635","url":null,"abstract":"<div><h3>Background and aims</h3><div>The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood.</div></div><div><h3>Methods and Results</h3><div>Using human transcriptome datasets to find genes co-regulated with <em>MTTP</em>, we identified <em>ERICH4</em> as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between <em>ERICH4</em> and plasma lipids. To validate <em>ERICH4</em> as a lipid gene, we generated whole-body <em>Erich4</em> knockout (<em>Erich4</em><sup><em>−/−</em></sup>) mice. ERICH4 deficiency<em>,</em> however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either.</div></div><div><h3>Conclusions</h3><div>Despite prediction tools indicating <em>ERICH4</em> as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118635"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.atherosclerosis.2024.118631
Daniel Goeder , Julia Maria Kröpfl , Thomas Angst , Henner Hanssen , Christoph Hauser , Denis Infanger , Debbie Maurer , Renate Oberhoffer-Fritz , Arno Schmidt-Trucksäss , Karsten Königstein
Background and aims
Endothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50 % of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs).
Methods
Sedentary adults with elevated CV risk between 40 and 60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n = 30) or received standard exercise recommendations (n = 14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses.
Results
baFMD improved by 2.38 % (CI:0.70–4.06, p = 0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2 % of dataset variability was higher in the NLPE-group compared to the control group (2.71 ± 2.02 vs. 1.65 ± 0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD.
Conclusions
The improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.
{"title":"VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial","authors":"Daniel Goeder , Julia Maria Kröpfl , Thomas Angst , Henner Hanssen , Christoph Hauser , Denis Infanger , Debbie Maurer , Renate Oberhoffer-Fritz , Arno Schmidt-Trucksäss , Karsten Königstein","doi":"10.1016/j.atherosclerosis.2024.118631","DOIUrl":"10.1016/j.atherosclerosis.2024.118631","url":null,"abstract":"<div><h3>Background and aims</h3><div>Endothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50 % of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs).</div></div><div><h3>Methods</h3><div>Sedentary adults with elevated CV risk between 40 and 60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n = 30) or received standard exercise recommendations (n = 14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses.</div></div><div><h3>Results</h3><div>baFMD improved by 2.38 % (CI:0.70–4.06, <em>p</em> = 0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2 % of dataset variability was higher in the NLPE-group compared to the control group (2.71 ± 2.02 <em>vs.</em> 1.65 ± 0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD.</div></div><div><h3>Conclusions</h3><div>The improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118631"},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.atherosclerosis.2024.118626
Joseph Heaton , Abbas Alshami , Steven Imburgio , Vandan Upadhyaya , Matthew Saybolt , Renato Apolito , Riple Hansalia , Jeffrey Selan , Jesus Almendral , Brett Sealove
Background and aims
Effective hypercholesterolemia management is linked to lower all-cause and cardiovascular mortality. The 2018 AHA/ACC guidelines recommended using the Pooled Cohort Equations (PCE) for lipid management, but these may overestimate risk and be less accurate for certain racial groups. The AHA's new PREVENT equation, which omits race and includes cardiometabolic factors, aims to provide a more accurate risk assessment for a diverse population. However, it has not yet been applied to a nationally representative US population, and implementation guidelines are still lacking. Our study aimed to evaluate potential changes in hypercholesterolemia management for primary prevention by using the PREVENT equation instead of the PCE.
Methods
Analyzing pre-pandemic NHANES 2017–2020 data, participants aged 40–75 without prior lipid-lowering treatment or other compelling indication were identified for elevated risk (≥7.5 %) using the PCE and PREVENT equations. We assessed risk shifts and indications for statin therapy, comparing the two risk equations. NHANES guidelines with weighting were followed to obtain US nationally representative estimates.
Results
Out of 77, 647, 807 (unweighted = 2494) participants, 81.0 % had no change in risk. The PCE flagged 18.8 % (n = 14,614,094) of participants at elevated risk not identified by PREVENT, while 0.20 % (n = 107,813) were flagged only by PREVENT. Participants identified solely by the PCE were older, with higher systolic blood pressure and increased estimated glomerular filtration rates.
Indications for statin therapy were largely unchanged (81.0 %). PREVENT newly identified (0.20 %) for moderate-intensity therapy and none for high-intensity therapy. Participants qualifying for moderate intensity therapy by the PCE were reclassified to no therapy in 74.59 % of cases, while 25.41 % remained unchanged. Participants qualifying for high-intensity therapy by the PCE were reclassified to moderate therapy in 93.97 % of cases, and 6.03 % were reclassified to no therapy.
Conclusions
The PREVENT equation notably differs in identifying hypercholesterolemia candidates compared to the PCE. Its adoption would influence cardiovascular risk reduction therapy recommendations, emphasizing the need for comprehensive studies to understand its long-term impact and reevaluate the threshold of treatment strategies for improved patient outcomes.
{"title":"Comparison of pooled cohort equation and PREVENT™ risk calculator for statin treatment allocation","authors":"Joseph Heaton , Abbas Alshami , Steven Imburgio , Vandan Upadhyaya , Matthew Saybolt , Renato Apolito , Riple Hansalia , Jeffrey Selan , Jesus Almendral , Brett Sealove","doi":"10.1016/j.atherosclerosis.2024.118626","DOIUrl":"10.1016/j.atherosclerosis.2024.118626","url":null,"abstract":"<div><h3>Background and aims</h3><div>Effective hypercholesterolemia management is linked to lower all-cause and cardiovascular mortality. The 2018 AHA/ACC guidelines recommended using the Pooled Cohort Equations (PCE) for lipid management, but these may overestimate risk and be less accurate for certain racial groups. The AHA's new PREVENT equation, which omits race and includes cardiometabolic factors, aims to provide a more accurate risk assessment for a diverse population. However, it has not yet been applied to a nationally representative US population, and implementation guidelines are still lacking. Our study aimed to evaluate potential changes in hypercholesterolemia management for primary prevention by using the PREVENT equation instead of the PCE.</div></div><div><h3>Methods</h3><div>Analyzing pre-pandemic NHANES 2017–2020 data, participants aged 40–75 without prior lipid-lowering treatment or other compelling indication were identified for elevated risk (≥7.5 %) using the PCE and PREVENT equations. We assessed risk shifts and indications for statin therapy, comparing the two risk equations. NHANES guidelines with weighting were followed to obtain US nationally representative estimates.</div></div><div><h3>Results</h3><div>Out of 77, 647, 807 (unweighted = 2494) participants, 81.0 % had no change in risk. The PCE flagged 18.8 % (n = 14,614,094) of participants at elevated risk not identified by PREVENT, while 0.20 % (n = 107,813) were flagged only by PREVENT. Participants identified solely by the PCE were older, with higher systolic blood pressure and increased estimated glomerular filtration rates.</div><div>Indications for statin therapy were largely unchanged (81.0 %). PREVENT newly identified (0.20 %) for moderate-intensity therapy and none for high-intensity therapy. Participants qualifying for moderate intensity therapy by the PCE were reclassified to no therapy in 74.59 % of cases, while 25.41 % remained unchanged. Participants qualifying for high-intensity therapy by the PCE were reclassified to moderate therapy in 93.97 % of cases, and 6.03 % were reclassified to no therapy.</div></div><div><h3>Conclusions</h3><div>The PREVENT equation notably differs in identifying hypercholesterolemia candidates compared to the PCE. Its adoption would influence cardiovascular risk reduction therapy recommendations, emphasizing the need for comprehensive studies to understand its long-term impact and reevaluate the threshold of treatment strategies for improved patient outcomes.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118626"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.atherosclerosis.2024.118625
Sofie B. Simony , Anne Langsted , Martin B. Mortensen , Børge G. Nordestgaard , Shoaib Afzal
Background and aims
Statin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction.
Methods
In a nationwide study, including 66,896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI versus non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction.
Results
Odds ratios for STEMI versus non-STEMI were 0.81 (95 % CI:0.77–0.85) and 1.07 (1.01–1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87–1.07) for <2 statin-years, 0.87 (0.79–0.95) for 2–4.9 statin-years, 0.80 (0.74–0.87) for 5–10 statin-years, and 0.75 (0.70–0.80) for >10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84–0.95) for low-intensity, 0.77 (0.73–0.82) for moderate-intensity, and 0.70 (0.63–0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI versus non-STEMI was 2.24 (2.13–2.37).
Conclusions
In this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions.
{"title":"Statin use is associated with less ST-elevation versus non-ST-elevation myocardial infarction in a nationwide study","authors":"Sofie B. Simony , Anne Langsted , Martin B. Mortensen , Børge G. Nordestgaard , Shoaib Afzal","doi":"10.1016/j.atherosclerosis.2024.118625","DOIUrl":"10.1016/j.atherosclerosis.2024.118625","url":null,"abstract":"<div><h3>Background and aims</h3><div>Statin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction.</div></div><div><h3>Methods</h3><div>In a nationwide study, including 66,896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI <em>versus</em> non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction.</div></div><div><h3>Results</h3><div>Odds ratios for STEMI <em>versus</em> non-STEMI were 0.81 (95 % CI:0.77–0.85) and 1.07 (1.01–1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87–1.07) for <2 statin-years, 0.87 (0.79–0.95) for 2–4.9 statin-years, 0.80 (0.74–0.87) for 5–10 statin-years, and 0.75 (0.70–0.80) for >10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84–0.95) for low-intensity, 0.77 (0.73–0.82) for moderate-intensity, and 0.70 (0.63–0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI <em>versus</em> non-STEMI was 2.24 (2.13–2.37).</div></div><div><h3>Conclusions</h3><div>In this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118625"},"PeriodicalIF":4.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1016/j.atherosclerosis.2024.118622
Ziqi Zhou , Suze-Anne Korteland , Blanca Tardajos-Ayllon , Junxi Wu , Emily Chambers , Julia Weninck , Michael Simons , Mark Dunning , Torsten Schenkel , Mannekomba Diagbouga , Jolanda Wentzel , Maria Fragiadaki , Paul C. Evans
Background and aims
Physiological shear stress promotes vascular homeostasis by inducing protective molecules in endothelial cells (EC). However, physiological shear stress has been linked to atherosclerosis progression in some individuals with heightened cardiovascular risk. To address this apparent paradox, we hypothesized that diseased arteries may exhibit reduced responsiveness to the protective effects of physiological shear stress. Consequently, we compared the transcriptome of EC exposed to physiological shear stress in healthy arteries versus atherosclerotic conditions.
Methods
Employing 3D light sheet imaging and computational fluid dynamics, we identified NOS3 as a marker of physiological shear stress in both healthy and atherosclerotic murine arteries. Single-cell RNA sequencing was performed on EC from healthy (C57BL/6) mice, mildly diseased (Apoe−/− normal diet) mice, and highly diseased (Apoe−/− high fat diet) mice. The transcriptomes of Nos3high cells (exposed to physiological shear stress) were compared among the groups.
Results
Nos3high EC were associated with several markers of physiological shear stress in healthy arteries. Clustering of Nos3high EC revealed 8 different EC subsets that varied in proportion between healthy and diseased arteries. Cluster-specific nested functional enrichment of gene ontology terms revealed that Nos3high EC in diseased arteries were enriched for inflammatory and apoptotic gene expression. These alterations were accompanied by changes in several mechanoreceptors, including the atheroprotective factor KLK10, which was enriched in Nos3high EC in healthy arteries but markedly reduced in severely diseased arteries.
Conclusions
Physiological shear stress is uncoupled from atheroprotective KLK10 within atherosclerotic plaques. This sheds light on the complex interplay between shear stress, endothelial function, and the progression of atherosclerosis in individuals at risk of cardiovascular complications.
{"title":"Shear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques","authors":"Ziqi Zhou , Suze-Anne Korteland , Blanca Tardajos-Ayllon , Junxi Wu , Emily Chambers , Julia Weninck , Michael Simons , Mark Dunning , Torsten Schenkel , Mannekomba Diagbouga , Jolanda Wentzel , Maria Fragiadaki , Paul C. Evans","doi":"10.1016/j.atherosclerosis.2024.118622","DOIUrl":"10.1016/j.atherosclerosis.2024.118622","url":null,"abstract":"<div><h3>Background and aims</h3><div>Physiological shear stress promotes vascular homeostasis by inducing protective molecules in endothelial cells (EC). However, physiological shear stress has been linked to atherosclerosis progression in some individuals with heightened cardiovascular risk. To address this apparent paradox, we hypothesized that diseased arteries may exhibit reduced responsiveness to the protective effects of physiological shear stress. Consequently, we compared the transcriptome of EC exposed to physiological shear stress in healthy arteries <em>versus</em> atherosclerotic conditions.</div></div><div><h3>Methods</h3><div>Employing 3D light sheet imaging and computational fluid dynamics, we identified NOS3 as a marker of physiological shear stress in both healthy and atherosclerotic murine arteries. Single-cell RNA sequencing was performed on EC from healthy (C57BL/6) mice, mildly diseased (<em>Apoe</em><sup><em>−/−</em></sup> normal diet) mice, and highly diseased (<em>Apoe</em><sup><em>−/−</em></sup> high fat diet) mice. The transcriptomes of <em>Nos3</em><sup>high</sup> cells (exposed to physiological shear stress) were compared among the groups.</div></div><div><h3>Results</h3><div><em>Nos3</em><sup>high</sup> EC were associated with several markers of physiological shear stress in healthy arteries. Clustering of <em>Nos3</em><sup>high</sup> EC revealed 8 different EC subsets that varied in proportion between healthy and diseased arteries. Cluster-specific nested functional enrichment of gene ontology terms revealed that <em>Nos3</em><sup>high</sup> EC in diseased arteries were enriched for inflammatory and apoptotic gene expression. These alterations were accompanied by changes in several mechanoreceptors, including the atheroprotective factor KLK10, which was enriched in <em>Nos3</em><sup>high</sup> EC in healthy arteries but markedly reduced in severely diseased arteries.</div></div><div><h3>Conclusions</h3><div>Physiological shear stress is uncoupled from atheroprotective KLK10 within atherosclerotic plaques. This sheds light on the complex interplay between shear stress, endothelial function, and the progression of atherosclerosis in individuals at risk of cardiovascular complications.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118622"},"PeriodicalIF":4.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1016/j.atherosclerosis.2024.118620
Alexander Vanmaele , Elke Bouwens , Sanne E. Hoeks , Alida Kindt , Lieke Lamont , Bram Fioole , Ricardo PJ. Budde , Sander ten Raa , Burhan Hussain , José Oliveira-Pinto , Arne S. Ijpma , Felix van Lier , K. Martijn Akkerhuis , Danielle F. Majoor-Krakauer , Jorg L. de Bruin , Thomas Hankemeier , Yolanda de Rijke , Hence JM. Verhagen , Eric Boersma , Isabella Kardys
Background and aims
Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans.
Methods
Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines.
Results
271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)).
Conclusions
Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.
{"title":"Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning","authors":"Alexander Vanmaele , Elke Bouwens , Sanne E. Hoeks , Alida Kindt , Lieke Lamont , Bram Fioole , Ricardo PJ. Budde , Sander ten Raa , Burhan Hussain , José Oliveira-Pinto , Arne S. Ijpma , Felix van Lier , K. Martijn Akkerhuis , Danielle F. Majoor-Krakauer , Jorg L. de Bruin , Thomas Hankemeier , Yolanda de Rijke , Hence JM. Verhagen , Eric Boersma , Isabella Kardys","doi":"10.1016/j.atherosclerosis.2024.118620","DOIUrl":"10.1016/j.atherosclerosis.2024.118620","url":null,"abstract":"<div><h3>Background and aims</h3><div>Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans.</div></div><div><h3>Methods</h3><div>Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines.</div></div><div><h3>Results</h3><div>271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)).</div></div><div><h3>Conclusions</h3><div>Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118620"},"PeriodicalIF":4.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atherosclerotic disease is a cholesterol-rich lipoprotein particle-driven disease resulting in the formation of atherosclerotic plaques in large and medium size arteries. Rupture or erosion of atherosclerotic plaques can trigger the formation of a thrombus causing the obstruction of the blood flow in the coronary artery and thereby leading to myocardial infarction (MI). Inflammation is a crucial pillar of the mechanisms leading to atherosclerosis and governing the cardiac repair post-MI. Dissecting the complex and sophisticated networks of the immune responses underlying the formation of atherosclerotic plaques and affecting the healing of the heart after MI will allow the designing of highly precise immunomodulatory therapies for these settings. Notably, MI also accelerates atherosclerosis via modulating the response of the immune system. Therefore, for the identification of effective and safe therapeutic targets, it is critical to consider the inflammatory continuum that interconnects the two pathologies and identify immunomodulatory strategies that confer a protective effect in both settings or at least, affect each pathology independently. Adaptive immunity, which consists of B and T lymphocytes, is a major regulator of atherosclerosis and post-MI cardiac repair. Here, we review and discuss the effect of potential adaptive immunity-targeting therapies, such as cell-depleting therapies, in atherosclerosis and post-MI cardiac injury.
动脉粥样硬化症是一种富含胆固醇的脂蛋白颗粒驱动的疾病，会在大中型动脉中形成动脉粥样硬化斑块。动脉粥样硬化斑块的破裂或侵蚀可引发血栓形成，导致冠状动脉血流受阻，从而引发心肌梗死（MI）。炎症是导致动脉粥样硬化和心肌梗塞后心脏修复机制的重要支柱。剖析动脉粥样硬化斑块形成和影响心肌梗塞后心脏愈合的复杂而精密的免疫反应网络，将有助于针对这些情况设计高度精确的免疫调节疗法。值得注意的是，心肌梗死也会通过调节免疫系统的反应加速动脉粥样硬化。因此，要确定有效、安全的治疗目标，就必须考虑将这两种病症相互关联的炎症连续体，并确定在两种情况下都能产生保护作用或至少能独立影响每种病症的免疫调节策略。由 B 淋巴细胞和 T 淋巴细胞组成的适应性免疫是动脉粥样硬化和心肌梗死后心脏修复的主要调节因素。在此，我们回顾并讨论了潜在的适应性免疫靶向疗法（如细胞损耗疗法）对动脉粥样硬化和心肌梗死后心脏损伤的影响。
{"title":"Targeting the adaptive immune continuum in atherosclerosis and post-MI injury","authors":"Viktoria Juhasz , Fiona T. Charlier , Tian X. Zhao , Dimitrios Tsiantoulas","doi":"10.1016/j.atherosclerosis.2024.118616","DOIUrl":"10.1016/j.atherosclerosis.2024.118616","url":null,"abstract":"<div><div>Atherosclerotic disease is a cholesterol-rich lipoprotein particle-driven disease resulting in the formation of atherosclerotic plaques in large and medium size arteries. Rupture or erosion of atherosclerotic plaques can trigger the formation of a thrombus causing the obstruction of the blood flow in the coronary artery and thereby leading to myocardial infarction (MI). Inflammation is a crucial pillar of the mechanisms leading to atherosclerosis and governing the cardiac repair post-MI. Dissecting the complex and sophisticated networks of the immune responses underlying the formation of atherosclerotic plaques and affecting the healing of the heart after MI will allow the designing of highly precise immunomodulatory therapies for these settings. Notably, MI also accelerates atherosclerosis via modulating the response of the immune system. Therefore, for the identification of effective and safe therapeutic targets, it is critical to consider the inflammatory continuum that interconnects the two pathologies and identify immunomodulatory strategies that confer a protective effect in both settings or at least, affect each pathology independently. Adaptive immunity, which consists of B and T lymphocytes, is a major regulator of atherosclerosis and post-MI cardiac repair. Here, we review and discuss the effect of potential adaptive immunity-targeting therapies, such as cell-depleting therapies, in atherosclerosis and post-MI cardiac injury.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118616"},"PeriodicalIF":4.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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