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Endocrine Disorders and Peripheral Arterial Disease - A Series of Reviews Cushing Syndrome-Cortisol Excess. 内分泌紊乱和外周动脉疾病——库欣综合征-皮质醇过量的一系列综述。
IF 2.8 3区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 DOI: 10.2174/0115701611272145231106053914
P Poredoš, G H Schernthaner, A Blinc, D P Mikhailidis, M Jensterle, P Anagnostis, P L Antignani, K Bajuk Studen, M Šabović, M K Ježovnik

Cushing syndrome (CS), characterised by endogenous or exogenous glucocorticoid hormone excess, is associated with several systemic complications, including impaired glucose metabolism, which often becomes clinically manifest as diabetes mellitus (DM). In addition, CS can harm the arterial wall because of hyperglycaemia, dyslipidaemia, hepatic steatosis, and central obesity. These metabolic disorders promote atherosclerosis by synthesising adipokines, leptin, and proinflammatory cytokines. Lower limb arterial complications in CS are common and significantly impact morbidity and mortality. Furthermore, CS, in combination with DM, is likely to cause more diffuse vascular disease that predominantly affects distal arterial beds. In conclusion, CS promotes atherosclerosis, including peripheral artery disease, by causing functional and morphological deterioration of the arterial vessel wall and increasing the presence of classical risk factors of atherosclerosis.

库欣综合征(CS)以内源性或外源性糖皮质激素过量为特征,与几种全身并发症相关,包括糖代谢受损,临床上常表现为糖尿病(DM)。此外,由于高血糖、血脂异常、肝脂肪变性和中枢性肥胖,CS可损害动脉壁。这些代谢紊乱通过合成脂肪因子、瘦素和促炎细胞因子促进动脉粥样硬化。下肢动脉并发症是常见的,并显著影响发病率和死亡率。此外,CS合并DM可能导致更多弥漫性血管疾病,主要影响远端动脉床。综上所述,CS通过引起动脉血管壁功能和形态的恶化,增加动脉粥样硬化经典危险因素的存在,促进动脉粥样硬化,包括外周动脉疾病。
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引用次数: 0
Effects of Tirofiban in Patients with Acute Myocardial Infarction and Diabetes Mellitus undergoing Primary Percutaneous Coronary Intervention. 替罗非班对接受初次经皮冠状动脉介入治疗的急性心肌梗死和糖尿病患者的影响。
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.2174/0115701611251882231012080210
Xiuying Tang, Runjun Li

Objective: This study evaluated the efficacy and safety of early vs. late tirofiban administration in the treatment of patients with acute ST-elevation myocardial infarction (STEMI) and diabetes mellitus (DM) undergoing primary percutaneous coronary intervention (pPCI).

Methods: 120 patients with STEMI and DM treated with pPCI were randomly divided into an observation group (n=60) and a control group (n=60). The observation group and the control group were intravenously injected with a bolus of tirofiban preoperatively or intraoperatively, respectively; both groups were then given an intravenous infusion over 24 h at 0.15 μg/kg/min. Thrombolysis in myocardial infarction (TIMI) grade flow, myocardial perfusion index, and functional heart parameters, as well as major adverse cardiovascular events and bleeding, were compared between the two groups.

Results: Functional heart parameters, including left ventricular ejection fraction and cardiac output, were significantly improved in the observation group 6 months after discharge. Thrombus aspiration, inflammatory factors, and cardiac troponin I (cTNI) were more significantly decreased in the observation group than in the control group. The sum-ST-segment elevation at 2 h after pPCI treatment in the observation group was better than that in the control group. There was no significant difference in the incidence of adverse reactions and bleeding between the two groups.

Conclusion: The administration of tirofiban before reperfusion therapy compared with after reperfusion therapy is more effective in reducing the hyperthrombotic load, thrombus aspiration, inflammatory factors, and cTNI and can effectively improve myocardial perfusion and heart function.

目的:本研究评估了早期和晚期替罗非班治疗急性ST段抬高型心肌梗死(STEMI)和糖尿病(DM)患者接受经皮冠状动脉介入治疗(pPCI)的疗效和安全性。方法:将120例经皮冠状动脉介入治疗的STEMI和DM患者随机分为观察组(n=60)和对照组(n=6 0)。观察组和对照组分别在术前或术中静脉注射替罗非班;然后,两组均以0.15µg/kg/min的速度静脉输注24小时。比较两组心肌梗死溶栓(TIMI)分级流量、心肌灌注指数、心脏功能参数以及主要心血管不良事件和出血情况。结果:观察组出院6个月后,包括左心室射血分数和心输出量在内的功能性心脏参数均有明显改善。与对照组相比,观察组的血栓抽吸、炎症因子和心肌肌钙蛋白I(cTNI)下降更为显著。观察组经皮冠状动脉介入治疗后2h ST段总抬高优于对照组。两组患者的不良反应和出血发生率无显著差异。结论:与再灌注后相比,再灌注前给予替罗非班在降低高血栓负荷、血栓抽吸、炎症因子和cTNI方面更有效,并能有效改善心肌灌注和心功能。
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引用次数: 0
P2Y12 Inhibitor or Aspirin Monotherapy in Patients with Coronary Artery Disease: is it Time for a Paradigm Shift? 冠状动脉疾病患者P2Y12抑制剂或阿司匹林单药治疗:是时候进行范式转变了吗?
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.2174/0115701611269735231106110250
Felice Gragnano, Antonio Capolongo, Paolo Calabrò
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引用次数: 0
Diagnostic Value of Serum Galectin-3 Binding Protein Level in Patients with Pulmonary Arterial Hypertension. 血清半乳糖凝集素-3结合蛋白水平对肺动脉高压的诊断价值。
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.2174/0115701611268078231010072521
Mingfei Li, Wenzhi Pan, Dan Tian, Dandan Chen, Xiaochun Zhang, Yuan Zhang, Shasha Chen, Daxin Zhou, Junbo Ge

Background: Pulmonary arterial hypertension (PAH) still lacks effective biomarkers to assist in its diagnosis and prognosis. Galectin-3 binding protein (Gal-3BP) plays a role in immune and inflammatory diseases.

Objective: This study aimed to evaluate Gal-3BP as a prognostic and predictive factor in patients with PAH.

Methods: From January 2017 to December 2019, we enrolled 167 consecutive PAH patients and 58 healthy controls. Right heart catheterization (RHC) was used to diagnose PAH. Serum Gal-3BP levels were measured by high-sensitivity human enzyme-linked immunosorbent assay (ELISA).

Results: Serum Gal-3BP levels in the PAH group were significantly higher compared with the control group (4.87±2.09 vs 2.22±0.86 μg/mL, p<0.001). Gal-3BP level was correlated with several hemodynamic parameters obtained from RHC (p<0.001). Multivariate linear regression analysis showed that Gal-3BP was a risk factor for PAH (odds ratio (OR)=2.947, 95% CI: 1.821-4.767, p<0.001). The optimal cut-off value of serum Gal-3BP level for predicting PAH was 2.89 μg/mL (area under the curve (AUC)=0.860, 95 % CI: 0.811-0.910, p<0.001). Kaplan-Meier analysis showed that Gal-3BP levels above the median (4.87 μg/mL) were associated with an increased risk of death in patients with PAH (hazard ratio (HR)=8.868, 95 % CI: 3.631-21.65, p<0.0001). Cox multivariate risk regression analysis showed that Gal-3BP was a risk factor for death in PAH patients (HR=2.779, 95 % CI: 1.823-4.237, p<0.001).

Conclusion: Serum Gal-3BP levels were increased in patients with PAH, and levels of Gal-3BP were associated with the severity of PAH. Gal-3BP might have predictive value for the diagnosis and prognosis of PAH.

背景:肺动脉高压(PAH)仍然缺乏有效的生物标志物来辅助其诊断和预后。半乳糖凝集素-3结合蛋白(Gal-3BP)在免疫和炎症性疾病中发挥作用。目的:本研究旨在评估Gal-3BP作为PAH患者的预后和预测因素。方法:2017年1月至2019年12月,我们招募了167名PAH患者和58名健康对照。采用右心导管(RHC)诊断PAH。采用高灵敏度人酶联免疫吸附试验(ELISA)检测血清Gal-3BP水平。结果:PAH组血清Gal-3BP水平显著高于对照组(4.87±2.09 vs 2.22±0.86 μg/mL)。结论:PAH患者血清Gal-3BP水平升高,且Gal-3BP水平与PAH严重程度相关。Gal-3BP可能对PAH的诊断和预后有预测价值。
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引用次数: 0
Study of Osteopontin as a Marker of Arteriovenous Shunt Stenosis in Hemodialysis Patients. 骨桥蛋白作为血液透析患者动静脉分流管狭窄标志物的研究。
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.2174/0115701611260120231106081701
Marwa R Elbarbary, Laila A Ahmed, Doaa A El-Adl, Alshimaa A Ezzat, Sherif A Nassib

Introduction: Although arteriovenous fistula (AVF) is the recommended access for hemodialysis (HD), it carries a high risk for stenosis. Since osteopontin (OPN) is implicated in the process of vascular calcification in HD patients, OPN may be a marker for AVF stenosis. The present study evaluated OPN as a potential marker of AVF stenosis in HD patients.

Methods: Diagnosing a stenotic lesion was made by combining B mode with color and pulse wave Doppler imaging. Criteria for diagnosis of stenotic AVF included 50% reduction in diameter in B mode in combination with a 2-3-fold increase of peak systolic velocity compared with the unaffected segment.

Results: The present study included 60 HD patients with stenotic AVF and 60 patients with functional AVF. Comparison between the two groups revealed that patients in the former group had significantly higher serum OPN levels [median (IQR): 17.1 (12.1-30.4) vs 5.8 (5.0-10.0) ng/mL, p<0.001]. All patients were classified into those with low (< median) and with high (≥ median) OPN levels. Comparison between these groups revealed that the former group had a significantly lower frequency of stenotic AVF (31.7 vs 68.3%, p<0.001) and a longer time to AVF stenosis [mean (95% CI): 68.4 (54.7-82.1) vs 46.5 (39.6-53.4) months, p=0.001].

Conclusion: OPN levels in HD patients may be useful markers for predicting and detecting AVF stenosis.

导读:虽然动静脉瘘(AVF)是血液透析(HD)的推荐途径,但它有很高的狭窄风险。由于骨桥蛋白(OPN)与HD患者的血管钙化过程有关,因此OPN可能是AVF狭窄的标志。本研究评估了OPN作为HD患者AVF狭窄的潜在标志。方法:B超结合彩色多普勒和脉搏波多普勒显像对狭窄病变进行诊断。狭窄性AVF的诊断标准包括B型内径缩小50%,同时与未受影响的节段相比,峰值收缩速度增加2-3倍。结果:本研究包括60例HD合并狭窄性AVF和60例功能性AVF。两组比较显示,前者患者血清OPN水平显著高于前者[中位数(IQR): 17.1 (12.1-30.4) vs 5.8 (5.0-10.0) ng/mL]。结论:HD患者的OPN水平可能是预测和检测AVF狭窄的有用指标。
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引用次数: 0
Beta-blockers in Hypertensive Left Ventricular Hypertrophy and Atrial Fibrillation Prevention. -受体阻滞剂在高血压左室肥厚和房颤预防中的作用。
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.2174/0115701611264647231110101700
Goran Koraćević, Sladjana Mićić, Milovan Stojanović, Marija Zdravkovic, Dragan Simić, Tomislav Kostić, Vesna Atanasković, Ružica Janković-Tomašević

Background: Hypertensive left ventricular hypertrophy (HTN LVH) is a key risk factor for atrial fibrillation (AF).

Objective: To evaluate the possible role of beta-blockers (BBs) in addition to a renin-angiotensinaldosterone system (RAAS) blocker in AF prevention in patients with HTN LVH.

Methods: We performed a PubMed, Elsevier, SAGE, Oxford, and Google Scholar search with the search items 'beta blocker hypertension left ventricular hypertrophy patient' from 2013-2023. In the end, a 'snowball search', based on the references of relevant papers as well as from papers that cited them was performed.

Results: HTN LVH is a risk factor for AF. In turn, AF substantially complicates HTN LVH and contributes to the genesis of heart failure (HF) with preserved ejection fraction (HFpEF). The prognosis of HFpEF is comparable with that of HF with reduced EF (HFrEF), and, regardless of the type, HF is associated with five-year mortality of 50-75%. The antiarrhythmic properties of BBs are wellrecognized, and BBs as a class of drugs are - in general - recommended to decrease the incidence of AF in HTN.

Conclusion: BBs are recommended (as a class) for AF prevention in several contemporary guidelines for HTN. LVH regression in HTN - used as a single criterion for the choice of antihypertensive medication - does not capture this protective effect. Consequently, it is worth studying how meaningful this antiarrhythmic action (to prevent AF) of BBs is in patients with HTN LVH in addition to a RAAS blocker.

背景:高血压性左心室肥厚(HTN LVH)是心房颤动(AF)的关键危险因素。目的:评价-受体阻滞剂(BBs)和肾素-血管紧张醛固酮系统(RAAS)阻滞剂在HTN LVH患者房颤预防中的可能作用。方法:我们对PubMed、Elsevier、SAGE、Oxford和Google Scholar进行了检索,检索条目为2013-2023年的“β受体阻滞剂高血压左心室肥厚患者”。最后,基于相关论文的参考文献以及引用它们的论文进行了“滚雪球搜索”。结果:HTN LVH是房颤的危险因素。反过来,房颤实质上使HTN LVH复杂化,并有助于发生心力衰竭(HF)并保留射血分数(HFpEF)。HFpEF的预后与EF降低的HF (HFrEF)相当,而且,无论哪种类型,HF与50-75%的5年死亡率相关。BBs的抗心律失常特性得到了广泛的认识,BBs作为一类药物通常被推荐用于降低HTN患者房颤的发生率。结论:在HTN的一些当代指南中,推荐使用BBs(作为一类)预防房颤。作为选择抗高血压药物的单一标准,LVH在HTN中的回归并没有体现出这种保护作用。因此,在HTN LVH患者中,除RAAS阻滞剂外,BBs抗心律失常(预防房颤)作用的意义值得研究。
{"title":"Beta-blockers in Hypertensive Left Ventricular Hypertrophy and Atrial Fibrillation Prevention.","authors":"Goran Koraćević, Sladjana Mićić, Milovan Stojanović, Marija Zdravkovic, Dragan Simić, Tomislav Kostić, Vesna Atanasković, Ružica Janković-Tomašević","doi":"10.2174/0115701611264647231110101700","DOIUrl":"10.2174/0115701611264647231110101700","url":null,"abstract":"<p><strong>Background: </strong>Hypertensive left ventricular hypertrophy (HTN LVH) is a key risk factor for atrial fibrillation (AF).</p><p><strong>Objective: </strong>To evaluate the possible role of beta-blockers (BBs) in addition to a renin-angiotensinaldosterone system (RAAS) blocker in AF prevention in patients with HTN LVH.</p><p><strong>Methods: </strong>We performed a PubMed, Elsevier, SAGE, Oxford, and Google Scholar search with the search items 'beta blocker hypertension left ventricular hypertrophy patient' from 2013-2023. In the end, a 'snowball search', based on the references of relevant papers as well as from papers that cited them was performed.</p><p><strong>Results: </strong>HTN LVH is a risk factor for AF. In turn, AF substantially complicates HTN LVH and contributes to the genesis of heart failure (HF) with preserved ejection fraction (HFpEF). The prognosis of HFpEF is comparable with that of HF with reduced EF (HFrEF), and, regardless of the type, HF is associated with five-year mortality of 50-75%. The antiarrhythmic properties of BBs are wellrecognized, and BBs as a class of drugs are - in general - recommended to decrease the incidence of AF in HTN.</p><p><strong>Conclusion: </strong>BBs are recommended (as a class) for AF prevention in several contemporary guidelines for HTN. LVH regression in HTN - used as a single criterion for the choice of antihypertensive medication - does not capture this protective effect. Consequently, it is worth studying how meaningful this antiarrhythmic action (to prevent AF) of BBs is in patients with HTN LVH in addition to a RAAS blocker.</p>","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458570","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}
引用次数: 0
Pharmacological Agents and Potential New Therapies in Pulmonary Arterial Hypertension. 肺动脉高压的药理作用和潜在新疗法。
IF 2.8 3区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 DOI: 10.2174/0115701611266576231211045731
Renata Trabach Santos, Maria Eduarda de Sá Freire Onofre, Dayene de Assis Fernandes Caldeira, Adriane Bello Klein, Patricia Rieken Macedo Rocco, Fernanda Ferreira Cruz, Pedro Leme Silva

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by an imbalance between vasoactive mediators, which causes vascular remodeling, increased pulmonary vascular resistance, and right ventricular overload, ultimately leading to heart failure and death. A metabolic theory has been suggested to explain the pathophysiology of PAH whereby abnormalities in mitochondrial biogenesis can trigger a hyperproliferative and apoptosis-resistant phenotype in cardiopulmonary and malignant cells, leading to mitochondrial dysfunction, which in turn causes the Warburg effect. This can culminate in the mitophagy of pulmonary vessels and cardiomyocytes. The present narrative review focuses on the pathophysiology of PAH, the pharmacological agents currently available for its treatment, and promising and challenging areas of therapeutic investigation.

肺动脉高压(PAH)是一种渐进性疾病,其特点是血管活性介质之间的失衡,导致血管重塑、肺血管阻力增加和右心室负荷过重,最终导致心力衰竭和死亡。有人提出了一种代谢理论来解释 PAH 的病理生理学,即线粒体生物生成异常可引发心肺细胞和恶性细胞的过度增殖和抗凋亡表型,导致线粒体功能障碍,进而引起沃伯格效应。最终导致肺血管和心肌细胞的有丝分裂。本综述重点介绍 PAH 的病理生理学、目前可用于治疗 PAH 的药理制剂,以及有希望和具有挑战性的治疗研究领域。
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引用次数: 0
Evaluation of Clinical, Echocardiographic, and Therapeutic Characteristics, and Prognostic Outcomes of Coexisting Heart Failure among Patients with Atrial Fibrillation: The Jordan Atrial Fibrillation (JoFib) Study. 评价心房颤动患者并发心力衰竭的临床、超声心动图、治疗特点和预后:约旦心房颤动(JoFib)研究
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2024-01-01 DOI: 10.2174/0115701611260211231115094716
Nasr Alrabadi, Mohammed Al-Nusair, Farah K El-Zubi, Mais Tashtoush, Osama Alzoubi, Sa'ed Khamis, Majd M Masadeh, Karem H Alzoubi, Mohammed Al-Hiari, Ayman Hammoudeh

Background: Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia in clinical practice. Heart failure (HF) can occur concurrently with AF.

Aim: We compared different demographic, clinical, and echocardiographic characteristics between patients with AF+HF and patients with AF only. Furthermore, we explored whether concurrent HF independently predicts several outcomes (all-cause mortality, cardiovascular mortality, ischemic stroke/systemic embolism (IS/SE), major bleeding, and clinically relevant non-major bleeding (CRNMB)).

Materials and methods: Comparisons between the AF+HF and the AF-only group were carried out. Multivariable Cox proportional hazard models were constructed for each outcome to assess whether HF was predictive of any of them while controlling for possible confounding factors.

Results: A total of 2020 patients were included in this study: 481 had AF+HF; 1539 had AF only. AF+HF patients were older, more commonly males, and had a higher prevalence of diabetes mellitus, dyslipidemia, coronary artery disease, and chronic kidney disease (p≤0.05). Furthermore, AF+HF patients more commonly had pulmonary hypertension and low ejection fraction (p≤0.001). Finally, HF was independently predictive of all-cause mortality (adjusted HR 2.17, 95% CI (1.66-2.85) and cardiovascular mortality (adjusted HR 2.37, 95% CI (1.68-3.36).

Conclusion: Coexisting AF+HF was associated with a more labile and higher-risk population among Jordanian patients. Furthermore, coexisting HF independently predicted higher all-cause mortality and cardiovascular mortality. Efforts should be made to efficiently identify such cases early and treat them aggressively.

背景:房颤(AF)是临床上最常见的心律失常。心衰(HF)可并发AF。目的:比较AF+HF患者和单纯AF患者的人口学、临床和超声心动图特征。此外,我们探讨了并发心衰是否能独立预测几种结局(全因死亡率、心血管死亡率、缺血性卒中/全身栓塞(IS/SE)、大出血和临床相关的非大出血(CRNMB))。材料与方法:将AF+HF组与AF组进行比较。在控制可能的混杂因素的同时,为每个结局构建多变量Cox比例风险模型,以评估HF是否能预测其中任何一个结局。结果:本研究共纳入2020例患者:481例AF+HF;1539只有AF。AF+HF患者年龄较大,男性居多,糖尿病、血脂异常、冠状动脉疾病、慢性肾脏疾病患病率较高(p≤0.05)。此外,AF+HF患者更常见的肺动脉高压和低射血分数(p≤0.001)。最后,心衰可独立预测全因死亡率(校正HR 2.17, 95% CI(1.66-2.85))和心血管死亡率(校正HR 2.37, 95% CI(1.68-3.36))。结论:在约旦患者中,并发AF+HF与更不稳定和高风险人群相关。此外,共存心衰独立预测更高的全因死亡率和心血管死亡率。应该努力尽早有效地发现这些病例并积极治疗。
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引用次数: 0
Lipoprotein (a) as a Biomarker for Cardiovascular Diseases and Potential New Therapies to Mitigate Risk 作为心血管疾病生物标志物的脂蛋白(a)和降低风险的潜在新疗法
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-12-23 DOI: 10.2174/0115701611267835231210054909
Debabrata Mukherjee, Steven E Nissen
Background: Lipoprotein (a) [Lp(a)] is a molecule that induces inflammation of the blood vessels, atherogenesis, valvular calcification, and thrombosis. Methods: We review the available evidence that suggests that high Lp(a) levels are associated with a persisting risk for atherosclerotic cardiovascular diseases despite optimization of established risk factors, including low-density lipoprotein cholesterol (LDL-C) levels. Observations: Approximately a quarter of the world population have Lp(a) levels of >50 mg/dL (125 nmol/L), a level associated with elevated cardiovascular risk. Lifestyle modification, statins, and ezetimibe do not effectively lower Lp(a) levels, while proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors and niacin only lower Lp(a) levels modestly. We describe clinical studies suggesting that gene silencing therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotide targeting Lp(a), offer a targeted approach with the potential for safe and robust Lp(a)- lowering with only a few doses (3-4) per year. Prospective randomized phase 3 studies are ongoing to validate safety, effectiveness in improving hard clinical outcomes, and tolerability to assess these therapies. Conclusion: Several emerging treatments with robust Lp(a)-lowering effects may significantly lower atherosclerotic cardiovascular risk.
背景:脂蛋白(a)[Lp(a)]是一种可诱发血管炎症、动脉粥样硬化、瓣膜钙化和血栓形成的分子。方法:我们回顾了现有证据,这些证据表明,尽管低密度脂蛋白胆固醇(LDL-C)水平等既定风险因素已得到优化,但高 Lp(a)水平与动脉粥样硬化性心血管疾病的持续风险相关。观察结果全球约有四分之一的人脂蛋白(a)水平为 50 毫克/分升(125 毫摩尔/升),这一水平与心血管风险升高有关。改变生活方式、他汀类药物和依折麦布不能有效降低脂蛋白(a)水平,而蛋白转换酶亚基酶/kexin 9 型(PCSK-9)抑制剂和烟酸只能适度降低脂蛋白(a)水平。我们描述的临床研究表明,基因沉默疗法,如针对脂蛋白(a)的小干扰 RNA(siRNA)和反义寡核苷酸,提供了一种有针对性的方法,每年只需服用几剂(3-4 剂)就有可能安全、稳健地降低脂蛋白(a)。目前正在进行前瞻性随机 3 期研究,以验证这些疗法的安全性、对改善硬性临床结果的有效性和耐受性。结论几种新出现的具有显著降低脂蛋白(a)效果的疗法可大大降低动脉粥样硬化性心血管疾病的风险。
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引用次数: 0
Dapagliflozin Alleviates Myocardial Ischaemia Reperfusion Injury by Activating Mitophagy via the AMPK-PINK1/Parkin Signalling Pathway 达帕格列净通过 AMPK-PINK1/Parkin 信号通路激活有丝分裂,从而缓解心肌缺血再灌注损伤
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-12-23 DOI: 10.2174/0115701611269801231211104905
Wei Zuo, Liang Wang, Ran Tian, Lun Wang, Yifan Liu, Hao Qian, Xinglin Yang, Zhenyu Liu
Introduction:: Myocardial ischaemia reperfusion injury (MIRI) determines infarct size and long-term outcomes after acute myocardial infarction (AMI). Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, alleviates MIRI in animal models. Method:: We investigated the potential mechanisms underlying the cardioprotective effect of dapagliflozin against MIRI, focusing on mitochondrial injury and mitophagy. MIRI mouse and H9C2 cell models were established. Results:: 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed a significant alleviation of MIRI after pre-treatment of dapagliflozin compared to the model group (14.91±1.76 vs. 40.47±3.69%). Data from the pre-treatment dapagliflozin group showed a significant decrease in left ventricular ejection fraction (LVEF) (44.8±2.7 vs. 28.5±5.3%, P<0.01), left ventricular end-diastolic volume (LVEDV) (70.6±9.5 vs. 93.5±13.8 ul, P<0.05), and left ventricular end-systolic volume (LVESV) (39.0± 8.3 vs. 67.9±13.7 ul, P<0.05) compared to the model group. Dapagliflozin also reduced the levels of reactive oxygen species (ROS) and fragmented mitochondrial DNA, reversed the decrease in mitochondrial membrane potential, and suppressed apoptosis. Further study showed that dapagliflozin could protect against mitochondrial injury by rapidly clearing damaged mitochondria via mitophagy in a phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/parkindependent manner. Dapagliflozin regulated mitophagy in cardiomyocytes by suppressing the adenosine 5’monophosphate-activated protein kinase (AMPK)-PINK1/parkin signalling pathway, resulting in attenuated MIRI. Conclusion:: Dapagliflozin alleviated MIRI by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.
导言心肌缺血再灌注损伤(MIRI)决定了急性心肌梗死(AMI)后的梗死面积和长期预后。钠-葡萄糖共转运体 2 抑制剂达帕格列酮可减轻动物模型中的 MIRI。方法:我们研究了达帕格列净对 MIRI 的心脏保护作用的潜在机制,重点是线粒体损伤和有丝分裂。建立了 MIRI 小鼠和 H9C2 细胞模型。结果2,3,5-三苯基氯化四氮唑(TTC)染色显示,与模型组相比,预处理达帕格列净后 MIRI 明显减轻(14.91±1.76 vs. 40.47±3.69%)。治疗前达帕格列净组的数据显示,左室射血分数(LVEF)显著下降(44.8±2.7 vs. 28.5±5.3%,P<0.01)、左室舒张末期容积(LVEDV)(70.6±9.5 vs. 93.5±13.8 ul,P<0.05)和左室收缩末期容积(LVESV)(39.0±8.3 vs. 67.9±13.7 ul,P<0.05)与模型组相比均显著下降。达帕格列净还降低了活性氧(ROS)和线粒体DNA碎片的水平,逆转了线粒体膜电位的下降,抑制了细胞凋亡。进一步的研究表明,达帕格列净可以保护线粒体免受损伤,因为它可以通过磷酸酶和天丝同源物(PTEN)诱导的假定激酶1(PINK1)/park依赖性方式,通过线粒体吞噬迅速清除受损的线粒体。达帕格列净通过抑制 5'单磷酸腺苷激活的蛋白激酶(AMPK)-PINK1/parkin 信号通路来调节心肌细胞的有丝分裂,从而导致 MIRI 的减弱。结论达帕格列净通过AMPK-PINK1/parkin信号通路激活有丝分裂,从而缓解了MIRI。
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Current vascular pharmacology
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