Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, 410011, Hunan, China.
Department of Cardiology, Hunan Children's Hospital, No. 86 Ziyuan Road, Yuhua District, Changsha, 410007, Hunan, China.
Cardiovasc Drugs Ther. 2021 Aug;35(4):815-828. doi: 10.1007/s10557-020-07007-8.
Substantial research has demonstrated the association between cardiovascular disease and the dysregulation of intracellular calcium, ageing, reduction in nicotinamide adenine dinucleotide NAD+ content, and decrease in sirtuin activity. CD38, which comprises the soluble type, type II, and type III, is the main NADase in mammals. This molecule catalyses the production of cyclic adenosine diphosphate ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and adenosine diphosphate ribose (ADPR), which stimulate the release of Ca, accompanied by NAD+ consumption and decreased sirtuin activity. Therefore, the relationship between cardiovascular disease and CD38 has been attracting increased attention. In this review, we summarize the structure, regulation, function, targeted drug development, and current research on CD38 in the cardiac context. More importantly, we provide original views about the as yet elusive mechanisms of CD38 action in certain cardiovascular disease models. Based on our review, we predict that CD38 may serve as a novel therapeutic target in cardiovascular disease in the future.
大量研究表明，细胞内钙的失调、衰老、烟酰胺腺嘌呤二核苷酸（NAD+）含量的减少以及沉默调节蛋白（Sirtuin）活性的降低与心血管疾病之间存在关联。CD38 包括可溶性型、II 型和 III 型，是哺乳动物中主要的 NAD 水解酶。该分子可催化环腺苷酸二磷酸核糖（cADPR）、烟酰胺腺嘌呤二核苷酸磷酸（NAADP）和二磷酸腺苷核糖（ADPR）的生成，从而刺激 Ca 的释放，同时消耗 NAD+并降低 Sirtuin 活性。因此，心血管疾病与 CD38 之间的关系引起了越来越多的关注。在这篇综述中，我们总结了 CD38 在心脏环境中的结构、调节、功能、靶向药物开发和当前研究。更重要的是，我们对某些心血管疾病模型中 CD38 作用的难以捉摸的机制提供了独到的见解。基于我们的综述，我们预测 CD38 可能成为未来心血管疾病的一种新的治疗靶点。
