多聚二磷酸腺苷聚合酶1与动脉粥样硬化

心血管疾病已经成为发达国家威胁生命的主要疾病，而动脉粥样硬化是最常见的心血管疾病之一．近来研究发现，多聚二磷酸腺苷聚合酶1(PARP1)在动脉粥样硬化致病机理中起着重要的作用．PARP1为PARP家族中含量最丰富的核酶，担负着DNA缺口敏感酶的功能，具有双向作用．正常情况下，它参与DNA损伤的修复，但过量激活则消耗NAD⁺和ATP使细胞功能紊乱，最终坏死．一些疾病的细胞程序性死亡机制可能与此相关，这些疾病包括动脉粥样硬化、冠心病、糖尿病及相关的心血管功能紊乱．有趣的是，除DNA损伤激活PARP1外，最近又发现激酶、多胺、咖啡因代谢物、茶碱和四环素等也可以参与PARP1的调节，核因子(NF-κB)和细胞内Ca²⁺也参与PARP1的调节．本文总结了靶点PARP的生物功能和基本原理，动脉粥样硬化致病的可能机制以及PARP1对其调节的研究进展，将对动脉粥样硬化的研究提供有力帮助．

PARP1 and Atherosclerosis

Cardiovascular disease is the leading cause of death and illness in developed countries today.Atherosclerosis is one of the most frequently ecountered diseases in angiocardiopathy.A number of studies have recently shown that PARP1 plays an important role in the mechanism of atherosclerosis.PARP1,a member of the PARP enzyme family,is an abundant nuclear protein which functions as a DNA nick-sensor enzyme.Poly(ADP-ribosylation) contributes to DNA repair and to the maintenance of genomic stability under normal circumstance.Overactivation of PARP consumes NAD+ and consequently ATP,culminating in cell dysfunction or necrosis.This cellular suicide mechanism has been implicated in the pathomechanism of atherosclerosis,myocardial ischemia,diabetes,and diabetes-associated cardiovascular dysfunction.Interestingly,several new and unexpected regulators of PARP1 activation have been found,including kinases,polyamines,caffeine metabolites,theophyline,and tetracycline antibiotics.The intracellular Ca2+ and NF-κB also participate in the regulatory mechanism.This review summarizes the biological function and general principle of targeted PARP,the possible pathomechanism of atherosclerosis,and the latest progress of PARP1-regulated atherosclerosis,which will make great strides in the study of atherosclerosis.