Pub Date : 2024-09-18DOI: 10.3389/fcvm.2024.1417432
Joanna Rogozik, Marcin Grabowski, Renata Główczyńska
BackgroundFamilial hypercholesterolemia (FH) is a serious genetic condition that results in abnormally high levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream, significantly increasing the risk of early onset of cardiovascular disease. The heterozygous form of FH (HeFH) is widespread, affecting around 1 in 500 people worldwide.Case reportIn this clinical report, we present the case of a patient who suffers from HeFH due to a mutation in the LDL receptor (LDLR) gene. A woman exhibited intolerance to statin therapy and did not attain adequate reduction in low-density lipoprotein cholesterol (LDL-C) levels on ezetimibe monotherapy. Genetic testing confirmed the presence of a pathogenic variant for FH with the deletion of exons 7–14. The administration of alirocumab (a dose of 150 mg sc) as the primary therapy did not exhibit the desired therapeutic outcome. Consequently, the patient was given inclisiran therapy (a dose of 284 mg sc), which significantly reduced LDL cholesterol levels after 3 months of treatment and during the 1-year follow-up.ConclusionInclisiran therapy has shown promising results for individuals with HeFH who experience statin intolerance. This therapy works by using a small interfering RNA (siRNA) to target the mRNA of proprotein convertase subtilisin/kexin type 9 (PCSK9), which leads to a significant reduction of LDL-C levels. This approach can be an alternative for patients without significant reductions in LDL-C levels with PCSK9 inhibitor therapy. For HeFH patients with limited treatment options due to statin intolerance and genetic mutations, inclisiran can represent a promising therapeutic option.
{"title":"Challenges in the management of familial hypercholesterolemia: a case report","authors":"Joanna Rogozik, Marcin Grabowski, Renata Główczyńska","doi":"10.3389/fcvm.2024.1417432","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1417432","url":null,"abstract":"BackgroundFamilial hypercholesterolemia (FH) is a serious genetic condition that results in abnormally high levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream, significantly increasing the risk of early onset of cardiovascular disease. The heterozygous form of FH (HeFH) is widespread, affecting around 1 in 500 people worldwide.Case reportIn this clinical report, we present the case of a patient who suffers from HeFH due to a mutation in the LDL receptor (LDLR) gene. A woman exhibited intolerance to statin therapy and did not attain adequate reduction in low-density lipoprotein cholesterol (LDL-C) levels on ezetimibe monotherapy. Genetic testing confirmed the presence of a pathogenic variant for FH with the deletion of exons 7–14. The administration of alirocumab (a dose of 150 mg sc) as the primary therapy did not exhibit the desired therapeutic outcome. Consequently, the patient was given inclisiran therapy (a dose of 284 mg sc), which significantly reduced LDL cholesterol levels after 3 months of treatment and during the 1-year follow-up.ConclusionInclisiran therapy has shown promising results for individuals with HeFH who experience statin intolerance. This therapy works by using a small interfering RNA (siRNA) to target the mRNA of proprotein convertase subtilisin/kexin type 9 (PCSK9), which leads to a significant reduction of LDL-C levels. This approach can be an alternative for patients without significant reductions in LDL-C levels with PCSK9 inhibitor therapy. For HeFH patients with limited treatment options due to statin intolerance and genetic mutations, inclisiran can represent a promising therapeutic option.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fcvm.2024.1425817
Yu Chen, Si Lu, Yong Ren, Jun Fan, Chun-Ping Bao, Xin Zhang, Yan-Kun Shi, Yan Wang, Li-Xia Yang
BackgroundAcute Coronary Syndrome (ACS) continues to be a leading cause of death and illness worldwide. Differentiating stable from unstable coronary plaques is essential for enhancing patient outcomes. This research investigates the role of CD147 as a biomarker for plaque stability among coronary artery disease patients.MethodsThe study began with high-throughput sequencing of blood samples from six patients, divided equally between those with Stable Angina (SA) and Unstable Angina (UA), followed by bioinformatics analysis. Expanding upon these findings, the study included 31 SA patients and 30 patients with ACS, using flow cytometry to examine CD147 expression on platelets and monocytes. Additionally, logistic regression was utilized to integrate traditional risk factors and evaluate the predictive value of CD147 expression for plaque stability.ResultsInitial sequencing displayed a notable difference in CD147 expression between SA and UA groups, with a significant increase in UA patients. Further analysis confirmed that elevated platelet CD147 expression was strongly associated with unstable plaques (OR = 277.81, P < .001), after adjusting for conventional risk factors, whereas monocyte CD147 levels did not show a significant difference.ConclusionElevated CD147 expression on platelets is a crucial biomarker for identifying unstable coronary artery plaques, offering insights into patient risk stratification and the development of targeted treatment strategies. This underscores the pivotal role of molecular research in understanding and managing coronary artery disease, paving the way for improved clinical outcomes.
{"title":"Integrating genomic profiling to clinical data: assessing the impact of CD147 expression on plaque stability","authors":"Yu Chen, Si Lu, Yong Ren, Jun Fan, Chun-Ping Bao, Xin Zhang, Yan-Kun Shi, Yan Wang, Li-Xia Yang","doi":"10.3389/fcvm.2024.1425817","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1425817","url":null,"abstract":"BackgroundAcute Coronary Syndrome (ACS) continues to be a leading cause of death and illness worldwide. Differentiating stable from unstable coronary plaques is essential for enhancing patient outcomes. This research investigates the role of CD147 as a biomarker for plaque stability among coronary artery disease patients.MethodsThe study began with high-throughput sequencing of blood samples from six patients, divided equally between those with Stable Angina (SA) and Unstable Angina (UA), followed by bioinformatics analysis. Expanding upon these findings, the study included 31 SA patients and 30 patients with ACS, using flow cytometry to examine CD147 expression on platelets and monocytes. Additionally, logistic regression was utilized to integrate traditional risk factors and evaluate the predictive value of CD147 expression for plaque stability.ResultsInitial sequencing displayed a notable difference in CD147 expression between SA and UA groups, with a significant increase in UA patients. Further analysis confirmed that elevated platelet CD147 expression was strongly associated with unstable plaques (OR = 277.81, <jats:italic>P</jats:italic> &lt; .001), after adjusting for conventional risk factors, whereas monocyte CD147 levels did not show a significant difference.ConclusionElevated CD147 expression on platelets is a crucial biomarker for identifying unstable coronary artery plaques, offering insights into patient risk stratification and the development of targeted treatment strategies. This underscores the pivotal role of molecular research in understanding and managing coronary artery disease, paving the way for improved clinical outcomes.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.3389/fcvm.2024.1413827
Xuejia Guo, Ning Zhang, Na Wang, Yanyan Zhang, Ya Liu, Miaomiao Pei, Gaiqin Liu, Xinle Jia
IntroductionChemotherapy-induced cardiotoxicity poses a significant challenge in the treatment of breast cancer, potentially compromising both the efficacy of cancer therapy and cardiac health of patients. This study aimed to enhance the early detection of cardiotoxic effects by integrating advanced imaging modalities and biomarker analysis, thereby facilitating timely interventions to mitigate cardiac risk.MethodsA prospective cohort design was employed, enrolling breast cancer patients scheduled for potentially cardiotoxic chemotherapy regimens. The study utilized a comprehensive diagnostic toolkit, including echocardiography with strain imaging, cardiac MRI, and serial measurements of cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides.ResultsThe analysis revealed that subtle changes in myocardial strain parameters and early biomarker elevations were predictive of subsequent declines in left ventricular function, preceding conventional echocardiographic evidence of cardiotoxicity. Logistic regression analysis highlighted the additive predictive value of integrating biomarker data with advanced imaging findings to identify patients with the highest risk of significant cardiotoxicity.DiscussionThe study concluded that an integrated diagnostic approach, combining detailed imaging assessments with sensitive biomarker analysis, offers a superior strategy for the early detection of chemotherapy-induced cardiotoxicity in breast cancer patients. This proactive diagnostic strategy empowers clinicians to tailor cancer therapy more precisely, balancing oncologic efficacy with cardiovascular safety and underscores the importance of a multidisciplinary approach in the management of patients undergoing potentially cardiotoxic chemotherapy.
{"title":"Early detection of chemotherapy-induced cardiotoxicity in breast cancer patients: a comprehensive analysis using speckle tracking echocardiography","authors":"Xuejia Guo, Ning Zhang, Na Wang, Yanyan Zhang, Ya Liu, Miaomiao Pei, Gaiqin Liu, Xinle Jia","doi":"10.3389/fcvm.2024.1413827","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1413827","url":null,"abstract":"IntroductionChemotherapy-induced cardiotoxicity poses a significant challenge in the treatment of breast cancer, potentially compromising both the efficacy of cancer therapy and cardiac health of patients. This study aimed to enhance the early detection of cardiotoxic effects by integrating advanced imaging modalities and biomarker analysis, thereby facilitating timely interventions to mitigate cardiac risk.MethodsA prospective cohort design was employed, enrolling breast cancer patients scheduled for potentially cardiotoxic chemotherapy regimens. The study utilized a comprehensive diagnostic toolkit, including echocardiography with strain imaging, cardiac MRI, and serial measurements of cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides.ResultsThe analysis revealed that subtle changes in myocardial strain parameters and early biomarker elevations were predictive of subsequent declines in left ventricular function, preceding conventional echocardiographic evidence of cardiotoxicity. Logistic regression analysis highlighted the additive predictive value of integrating biomarker data with advanced imaging findings to identify patients with the highest risk of significant cardiotoxicity.DiscussionThe study concluded that an integrated diagnostic approach, combining detailed imaging assessments with sensitive biomarker analysis, offers a superior strategy for the early detection of chemotherapy-induced cardiotoxicity in breast cancer patients. This proactive diagnostic strategy empowers clinicians to tailor cancer therapy more precisely, balancing oncologic efficacy with cardiovascular safety and underscores the importance of a multidisciplinary approach in the management of patients undergoing potentially cardiotoxic chemotherapy.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundThe relationship between the triglyceride–glucose (TyG) index and no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute ST-segment elevation myocardial infarction (STEMI) remains unclear. This study aimed to investigate the relationship between baseline TyG index and no-reflow phenomenon in STEMI patients with T2DM after PCI.MethodsThis study enrolled 695 patients with T2DM and STEMI from the General Hospital of Ningxia Medical University (2014–2019). Patients were divided into tertiles according to the TyG index levels. The incidence of no-reflow phenomenon was recorded. A multivariate regression model was developed to analyze the association between the baseline TyG index and no-reflow phenomenon. The linear association between the baseline TyG index and no-reflow phenomenon was explored using smooth curve fitting with parallel subgroup analyses. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of the TyG index.ResultsA multivariate logistic regression model revealed that the TyG index was an independent risk factor of no-reflow phenomenon [OR = 3.23, 95%CI: 2.15–4.86, P < 0.001], and the occurrence of no-reflow phenomenon increased gradually with the increase of TyG index tertile interval (P < 0.001). Smooth curve fitting showed that the TyG index was linearly related to the risk of no-reflow. Subgroup analysis showed that they participated in this positive correlation. The area under the ROC curve (AUC) of the TyG index for evaluating the occurrence of no-reflow was 0.710 (95% CI: 0.640–0.780; P < 0.01).ConclusionsThe TyG index is independently associated with no-reflow phenomenon, suggesting that the simple index of the TyG index can be used for risk assessment of no-reflow phenomenon after PCI in STEMI patients with T2DM.
{"title":"The triglyceride–glucose index is associated with no-reflow phenomenon in STEMI patients with type 2 diabetes after percutaneous coronary intervention","authors":"Juan Ma, Peng Wu, Shengzong Ma, Xueping Ma, Ping Jin, Shaobin Jia","doi":"10.3389/fcvm.2024.1386318","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1386318","url":null,"abstract":"BackgroundThe relationship between the triglyceride–glucose (TyG) index and no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute ST-segment elevation myocardial infarction (STEMI) remains unclear. This study aimed to investigate the relationship between baseline TyG index and no-reflow phenomenon in STEMI patients with T2DM after PCI.MethodsThis study enrolled 695 patients with T2DM and STEMI from the General Hospital of Ningxia Medical University (2014–2019). Patients were divided into tertiles according to the TyG index levels. The incidence of no-reflow phenomenon was recorded. A multivariate regression model was developed to analyze the association between the baseline TyG index and no-reflow phenomenon. The linear association between the baseline TyG index and no-reflow phenomenon was explored using smooth curve fitting with parallel subgroup analyses. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of the TyG index.ResultsA multivariate logistic regression model revealed that the TyG index was an independent risk factor of no-reflow phenomenon [OR = 3.23, 95%CI: 2.15–4.86, <jats:italic>P</jats:italic> &lt; 0.001], and the occurrence of no-reflow phenomenon increased gradually with the increase of TyG index tertile interval (<jats:italic>P</jats:italic> &lt; 0.001). Smooth curve fitting showed that the TyG index was linearly related to the risk of no-reflow. Subgroup analysis showed that they participated in this positive correlation. The area under the ROC curve (AUC) of the TyG index for evaluating the occurrence of no-reflow was 0.710 (95% CI: 0.640–0.780; <jats:italic>P &lt; </jats:italic>0.01).ConclusionsThe TyG index is independently associated with no-reflow phenomenon, suggesting that the simple index of the TyG index can be used for risk assessment of no-reflow phenomenon after PCI in STEMI patients with T2DM.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fcvm.2024.1408351
Zhihao Xue, Sicheng Zhu, Fan Yang, Juan Gao, Hao Peng, Chao Zou, Hang Jin, Chenxi Hu
IntroductionHigh-resolution whole-heart coronary magnetic resonance angiography (CMRA) often suffers from unreasonably long scan times, rendering imaging acceleration highly desirable. Traditional reconstruction methods used in CMRA rely on either hand-crafted priors or supervised learning models. Although the latter often yield superior reconstruction quality, they require a large amount of training data and memory resources, and may encounter generalization issues when dealing with out-of-distribution datasets.MethodsTo address these challenges, we introduce an unsupervised reconstruction method that combines deep image prior (DIP) with compressed sensing (CS) to accelerate 3D CMRA. This method incorporates a slice-by-slice DIP reconstruction and 3D total variation (TV) regularization, enabling high-quality reconstruction under a significant acceleration while enforcing continuity in the slice direction. We evaluated our method by comparing it to iterative SENSE, CS-TV, CS-wavelet, and other DIP-based variants, using both retrospectively and prospectively undersampled datasets.ResultsThe results demonstrate the superiority of our 3D DIP-CS approach, which improved the reconstruction accuracy relative to the other approaches across both datasets. Ablation studies further reveal the benefits of combining DIP with 3D TV regularization, which leads to significant improvements of image quality over pure DIP-based methods. Evaluation of vessel sharpness and image quality scores shows that DIP-CS improves the quality of reformatted coronary arteries.DiscussionThe proposed method enables scan-specific reconstruction of high-quality 3D CMRA from a five-minute acquisition, without relying on fully-sampled training data or placing a heavy burden on memory resources.
导言高分辨率全心冠状动脉磁共振血管造影术（CMRA）往往存在扫描时间过长的问题，因此非常需要成像加速。用于 CMRA 的传统重建方法依赖于手工创建的先验或监督学习模型。为了应对这些挑战，我们引入了一种无监督重建方法，将深度图像先验（DIP）与压缩传感（CS）相结合，以加速 3D CMRA。该方法结合了逐片 DIP 重建和三维总变异（TV）正则化，在显著加速的情况下实现了高质量重建，同时确保了切片方向的连续性。我们使用回顾性和前瞻性欠采样数据集，将我们的方法与迭代 SENSE、CS-TV、CS-小波和其他基于 DIP 的变体进行了比较，从而对我们的方法进行了评估。消融研究进一步揭示了将 DIP 与 3D TV 正则化相结合的优势，与纯 DIP 方法相比，这种方法显著提高了图像质量。对血管锐利度和图像质量评分的评估表明，DIP-CS 提高了重新格式化冠状动脉的质量。 讨论所提出的方法可以在不依赖全采样训练数据或对内存资源造成沉重负担的情况下，从五分钟的采集数据中重建特定扫描的高质量 3D CMRA。
{"title":"A hybrid deep image prior and compressed sensing reconstruction method for highly accelerated 3D coronary magnetic resonance angiography","authors":"Zhihao Xue, Sicheng Zhu, Fan Yang, Juan Gao, Hao Peng, Chao Zou, Hang Jin, Chenxi Hu","doi":"10.3389/fcvm.2024.1408351","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1408351","url":null,"abstract":"IntroductionHigh-resolution whole-heart coronary magnetic resonance angiography (CMRA) often suffers from unreasonably long scan times, rendering imaging acceleration highly desirable. Traditional reconstruction methods used in CMRA rely on either hand-crafted priors or supervised learning models. Although the latter often yield superior reconstruction quality, they require a large amount of training data and memory resources, and may encounter generalization issues when dealing with out-of-distribution datasets.MethodsTo address these challenges, we introduce an unsupervised reconstruction method that combines deep image prior (DIP) with compressed sensing (CS) to accelerate 3D CMRA. This method incorporates a slice-by-slice DIP reconstruction and 3D total variation (TV) regularization, enabling high-quality reconstruction under a significant acceleration while enforcing continuity in the slice direction. We evaluated our method by comparing it to iterative SENSE, CS-TV, CS-wavelet, and other DIP-based variants, using both retrospectively and prospectively undersampled datasets.ResultsThe results demonstrate the superiority of our 3D DIP-CS approach, which improved the reconstruction accuracy relative to the other approaches across both datasets. Ablation studies further reveal the benefits of combining DIP with 3D TV regularization, which leads to significant improvements of image quality over pure DIP-based methods. Evaluation of vessel sharpness and image quality scores shows that DIP-CS improves the quality of reformatted coronary arteries.DiscussionThe proposed method enables scan-specific reconstruction of high-quality 3D CMRA from a five-minute acquisition, without relying on fully-sampled training data or placing a heavy burden on memory resources.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fcvm.2024.1448607
Jordan M. Bobek, Gage M. Stuttgen, Daisy Sahoo
IntroductionRecent findings demonstrate that high density lipoprotein (HDL) function rather than HDL-cholesterol levels themselves may be a better indicator of cardiovascular disease risk. One mechanism by which HDL can become dysfunctional is through oxidative modification by reactive aldehydes. Previous studies from our group demonstrated that HDL modified by reactive aldehydes alters select cardioprotective functions of HDL in macrophages. To identify mechanisms by which dysfunctional HDL contributes to atherosclerosis progression, we designed experiments to test the hypothesis that HDL modified by reactive aldehydes triggers endoplasmic reticulum (ER) stress in primary murine macrophages.Methods and resultsPeritoneal macrophages were harvested from wild-type C57BL/6J mice and treated with thapsigargin, oxLDL, and/or HDL for up to 48 hours. Immunoblot analysis and semi-quantitative PCR were used to measure expression of BiP, p-eIF2α, ATF6, and XBP1 to assess activation of the unfolded protein response (UPR). Through an extensive set of comprehensive experiments, and contrary to some published studies, our findings led us to three novel discoveries in primary murine macrophages: (i) oxLDL alone was unable to induce ER stress; (ii) co-incubation with oxLDL or HDL in the presence of thapsigargin had an additive effect in which expression of ER stress markers were significantly increased and prolonged as compared to cells treated with thapsigargin alone; and (iii) HDL, in the presence or absence of reactive aldehydes, was unable blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL.ConclusionsOur systematic approach to assess the role of native and modified HDL in mediating primary macrophage ER stress led to the discovery that lipoproteins on their own require the presence of thapsigargin to synergistically increase expression of ER stress markers. We further demonstrated that HDL, in the presence or absence of reactive aldehydes, was unable to blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL. Together, our findings suggest the need for more detailed investigations to better understand the role of native and modified lipoproteins in mediating ER stress pathways.
{"title":"A comprehensive analysis of the role of native and modified HDL in ER stress in primary macrophages","authors":"Jordan M. Bobek, Gage M. Stuttgen, Daisy Sahoo","doi":"10.3389/fcvm.2024.1448607","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1448607","url":null,"abstract":"IntroductionRecent findings demonstrate that high density lipoprotein (HDL) function rather than HDL-cholesterol levels themselves may be a better indicator of cardiovascular disease risk. One mechanism by which HDL can become dysfunctional is through oxidative modification by reactive aldehydes. Previous studies from our group demonstrated that HDL modified by reactive aldehydes alters select cardioprotective functions of HDL in macrophages. To identify mechanisms by which dysfunctional HDL contributes to atherosclerosis progression, we designed experiments to test the hypothesis that HDL modified by reactive aldehydes triggers endoplasmic reticulum (ER) stress in primary murine macrophages.Methods and resultsPeritoneal macrophages were harvested from wild-type C57BL/6J mice and treated with thapsigargin, oxLDL, and/or HDL for up to 48 hours. Immunoblot analysis and semi-quantitative PCR were used to measure expression of BiP, p-eIF2α, ATF6, and XBP1 to assess activation of the unfolded protein response (UPR). Through an extensive set of comprehensive experiments, and contrary to some published studies, our findings led us to three novel discoveries in primary murine macrophages: (i) oxLDL alone was unable to induce ER stress; (ii) co-incubation with oxLDL or HDL in the presence of thapsigargin had an additive effect in which expression of ER stress markers were significantly increased and prolonged as compared to cells treated with thapsigargin alone; and (iii) HDL, in the presence or absence of reactive aldehydes, was unable blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL.ConclusionsOur systematic approach to assess the role of native and modified HDL in mediating primary macrophage ER stress led to the discovery that lipoproteins on their own require the presence of thapsigargin to synergistically increase expression of ER stress markers. We further demonstrated that HDL, in the presence or absence of reactive aldehydes, was unable to blunt the ER stress induced by thapsigargin in the presence or absence of oxLDL. Together, our findings suggest the need for more detailed investigations to better understand the role of native and modified lipoproteins in mediating ER stress pathways.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.
{"title":"Research progress of exosomes from different sources in myocardial ischemia","authors":"Huan Yan, Huang Ding, Ruo-Xi Xie, Zhi-Qing Liu, Xiao-Qian Yang, Ling-Li Xie, Cai-Xia Liu, Xiao-Dan Liu, Li-Yuan Chen, Xiao-Ping Huang","doi":"10.3389/fcvm.2024.1436764","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1436764","url":null,"abstract":"Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fcvm.2024.1450252
Ziyan Wang, Pingyang Zhang
Atherosclerosis is a slow, progressive disease that is closely associated with major adverse cardiovascular events. Early diagnosis and risk assessment of atherosclerosis can effectively improve the prognosis and reduce the occurrence of adverse cardiovascular events in the later stage. A variety of invasive and non-invasive imaging modalities are important tools for diagnosing lesions, monitoring the efficacy of treatments, and predicting associated risk events. This review mainly introduces the four commonly used non-invasive imaging modalities in clinical practice and intravascular imaging such as optical coherence tomography, intravascular ultrasound imaging, and near-infrared spectroscopy, compares the advantages and disadvantages in the diagnosis of vulnerable plaques, and briefly summarizes the new progressions of each.
{"title":"Novel imaging modalities for the identification of vulnerable plaques","authors":"Ziyan Wang, Pingyang Zhang","doi":"10.3389/fcvm.2024.1450252","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1450252","url":null,"abstract":"Atherosclerosis is a slow, progressive disease that is closely associated with major adverse cardiovascular events. Early diagnosis and risk assessment of atherosclerosis can effectively improve the prognosis and reduce the occurrence of adverse cardiovascular events in the later stage. A variety of invasive and non-invasive imaging modalities are important tools for diagnosing lesions, monitoring the efficacy of treatments, and predicting associated risk events. This review mainly introduces the four commonly used non-invasive imaging modalities in clinical practice and intravascular imaging such as optical coherence tomography, intravascular ultrasound imaging, and near-infrared spectroscopy, compares the advantages and disadvantages in the diagnosis of vulnerable plaques, and briefly summarizes the new progressions of each.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fcvm.2024.1453127
Qiulian Lei, Zefei Jiang, Yu Shao, Xinghong Liu, Xiaoping Li
Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.
{"title":"Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation","authors":"Qiulian Lei, Zefei Jiang, Yu Shao, Xinghong Liu, Xiaoping Li","doi":"10.3389/fcvm.2024.1453127","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1453127","url":null,"abstract":"Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fcvm.2024.1417906
Li Chen, Jing Zhang, Chunquan Zhang
Metastasis to the left atrium is exceptionally uncommon, occurring at a rate of only 3.1%. The clinical manifestations of lung cancer metastasizing to the heart can vary widely. They range from paraneoplastic syndrome, dyspnea, and ST-segment elevation on an electrocardiogram to no clinically significant symptoms. Diverging from typical metastatic patterns observed in lung cancer, this case report presents a detailed description, from the perspective of the microenvironment, of a rare instance where lung cancer metastasized to the mediastinal lymph nodes, adrenal glands, brain, and notably, the left atrium, in a non-smoking female patient.
转移到左心房的肺癌并不常见，发生率仅为 3.1%。肺癌转移至心脏的临床表现差异很大。从副肿瘤综合征、呼吸困难、心电图 ST 段抬高到无临床症状不等。与肺癌的典型转移模式不同，本病例报告从微环境的角度详细描述了一名非吸烟女性患者肺癌转移至纵隔淋巴结、肾上腺、大脑，尤其是左心房的罕见病例。
{"title":"Case Report: Lung cancer with rare cardiac and other multiple metastases","authors":"Li Chen, Jing Zhang, Chunquan Zhang","doi":"10.3389/fcvm.2024.1417906","DOIUrl":"https://doi.org/10.3389/fcvm.2024.1417906","url":null,"abstract":"Metastasis to the left atrium is exceptionally uncommon, occurring at a rate of only 3.1%. The clinical manifestations of lung cancer metastasizing to the heart can vary widely. They range from paraneoplastic syndrome, dyspnea, and ST-segment elevation on an electrocardiogram to no clinically significant symptoms. Diverging from typical metastatic patterns observed in lung cancer, this case report presents a detailed description, from the perspective of the microenvironment, of a rare instance where lung cancer metastasized to the mediastinal lymph nodes, adrenal glands, brain, and notably, the left atrium, in a non-smoking female patient.","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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