心血管不可改变危险因素、合并症和并发症与缺血/再灌注损伤的相互作用以及药理学治疗和缺血条件下的心脏保护。

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2023-01-01 Epub Date: 2022-12-08 DOI:10.1124/pharmrev.121.000348
Péter Ferdinandy, Ioanna Andreadou, Gary F Baxter, Hans Erik Bøtker, Sean M Davidson, Dobromir Dobrev, Bernard J Gersh, Gerd Heusch, Sandrine Lecour, Marisol Ruiz-Meana, Coert J Zuurbier, Derek J Hausenloy, Rainer Schulz
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引用次数: 0

摘要

心肌的预处理、后处理和远程处理增强了心脏承受长时间缺血/再灌注损伤的能力,并有可能为心脏保护提供新的治疗模式。尽管在过去30年的实验研究中已经阐明了许多导致内源性心脏保护的信号通路,但市场上还没有针对该适应症的心脏保护药物。未能将心脏保护转化为患者益处的一个可能的主要原因是,在临床评估之前,缺乏对有前景的心脏保护疗法的严格和系统的临床前评估,因为人类缺血性心脏病是一种由心血管风险因素和共病引起或与之相关的复杂疾病。这些风险因素和合并症诱导细胞信号级联的基本改变,从而影响缺血/再灌注损伤的发展和对心脏保护干预的反应。此外,一些用于治疗这些合并症的药物可能会通过再次改变细胞信号通路来影响心脏保护。本文的目的是回顾最近的证据,即心血管风险因素、合并症及其药物可能会改变对心脏保护干预的反应。我们强调,在设计用于识别和验证心脏保护药物靶点和临床研究的临床前研究时,迫切需要考虑心血管风险因素的存在以及合并症及其伴随药物。这将有望最大限度地提高为大多数患有多种合并症的患者开发有效心脏保护疗法的合理方法的成功率。意义声明:缺血性心脏病是导致死亡的主要原因;然而,市场上仍然没有心脏保护药物。大多数关于心脏保护的研究都是在没有合并症的缺血/再灌注动物模型中进行的;然而,缺血性心脏病与其他系统性疾病(如高血压、高脂血症、糖尿病、动脉粥样硬化)一起发展。在这里,我们重点关注临床前和临床证据,表明这些合并症及其常规药物如何影响缺血/再灌注损伤并干扰心脏保护策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.

Preconditioning, postconditioning, and remote conditioning of the myocardium enhance the ability of the heart to withstand a prolonged ischemia/reperfusion insult and the potential to provide novel therapeutic paradigms for cardioprotection. While many signaling pathways leading to endogenous cardioprotection have been elucidated in experimental studies over the past 30 years, no cardioprotective drug is on the market yet for that indication. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigorous and systematic preclinical evaluation of promising cardioprotective therapies prior to their clinical evaluation, since ischemic heart disease in humans is a complex disorder caused by or associated with cardiovascular risk factors and comorbidities. These risk factors and comorbidities induce fundamental alterations in cellular signaling cascades that affect the development of ischemia/reperfusion injury and responses to cardioprotective interventions. Moreover, some of the medications used to treat these comorbidities may impact on cardioprotection by again modifying cellular signaling pathways. The aim of this article is to review the recent evidence that cardiovascular risk factors as well as comorbidities and their medications may modify the response to cardioprotective interventions. We emphasize the critical need for taking into account the presence of cardiovascular risk factors as well as comorbidities and their concomitant medications when designing preclinical studies for the identification and validation of cardioprotective drug targets and clinical studies. This will hopefully maximize the success rate of developing rational approaches to effective cardioprotective therapies for the majority of patients with multiple comorbidities. SIGNIFICANCE STATEMENT: Ischemic heart disease is a major cause of mortality; however, there are still no cardioprotective drugs on the market. Most studies on cardioprotection have been undertaken in animal models of ischemia/reperfusion in the absence of comorbidities; however, ischemic heart disease develops with other systemic disorders (e.g., hypertension, hyperlipidemia, diabetes, atherosclerosis). Here we focus on the preclinical and clinical evidence showing how these comorbidities and their routine medications affect ischemia/reperfusion injury and interfere with cardioprotective strategies.

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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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