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基因组学策略鉴定新型治疗靶点

Genomic Strategies Toward Identification of Novel Therapeutic Targets.

机构信息

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany.

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., partner site Munich Heart Alliance, Munich, Germany.

出版信息

Handb Exp Pharmacol. 2022;270:429-462. doi: 10.1007/164_2020_360.

Abstract

Coronary artery disease, myocardial infarction, and secondary damages of the myocardium in the form of ischemic heart disease remain major causes of death in Western countries. Beyond traditional risk factors such as smoking, hypertension, dyslipidemia, or diabetes, a positive family history is known to increase risk. The genetic factors underlying this observation remained unknown for decades until genetic studies were able to identify multiple genomic loci contributing to the heritability of the trait. Knowledge of the affected genes and the resulting molecular and cellular mechanisms leads to improved understanding of the pathophysiology leading to coronary atherosclerosis. Major goals are also to improve prevention and therapy of coronary artery disease and its sequelae via improved risk prediction tools and pharmacological targets. In this chapter, we recapitulate recent major findings. We focus on established novel targets and discuss possible further targets which are currently explored in translational studies.

摘要

冠心病、心肌梗死以及以缺血性心脏病形式出现的心肌继发性损伤仍然是西方国家主要的死亡原因。除了吸烟、高血压、血脂异常或糖尿病等传统危险因素外,阳性家族史也被认为会增加风险。几十年来,人们一直不知道导致这种观察结果的遗传因素,直到遗传研究能够确定多个基因组位点有助于该特征的遗传性。对受影响基因的了解以及由此产生的分子和细胞机制导致人们对导致冠状动脉粥样硬化的病理生理学有了更好的理解。主要目标还包括通过改进风险预测工具和药物靶点来改善冠心病及其后遗症的预防和治疗。在这一章中,我们总结了最近的主要发现。我们专注于已确立的新靶点,并讨论了目前在转化研究中探索的可能的进一步靶点。

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