Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
Baylor College of Medicine, One Baylor Plaza Blvd., Houston Texas, USA.
Oxid Med Cell Longev. 2021 Apr 29;2021:5529256. doi: 10.1155/2021/5529256. eCollection 2021.
Cardiovascular disorders (CVD) are highly prevalent and the leading cause of death worldwide. Atherosclerosis is responsible for most cases of CVD. The plaque formation and subsequent thrombosis in atherosclerosis constitute an ongoing process that is influenced by numerous risk factors such as hypertension, diabetes, dyslipidemia, obesity, smoking, inflammation, and sedentary lifestyle. Among the various risk and protective factors, the role of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common inborn enzyme disorder across populations, is still debated. For decades, it has been considered a protective factor against the development of CVD. However, in the recent years, growing scientific evidence has suggested that this inherited condition may act as a CVD risk factor. The role of G6PD deficiency in the atherogenic process has been investigated using in vitro or ex vivo cellular models, animal models, and epidemiological studies in human cohorts of variable size and across different ethnic groups, with conflicting results. In this review, the impact of G6PD deficiency on CVD was critically reconsidered, taking into account the most recent acquisitions on molecular and biochemical mechanisms, namely, antioxidative mechanisms, glutathione recycling, and nitric oxide production, as well as their mutual interactions, which may be impaired by the enzyme defect in the context of the pentose phosphate pathway. Overall, current evidence supports the notion that G6PD downregulation may favor the onset and evolution of atheroma in subjects at risk of CVD. Given the relatively high frequency of this enzyme deficiency in several regions of the world, this finding might be of practical importance to tailor surveillance guidelines and facilitate risk stratification.
心血管疾病（CVD）是全球高发且致死的主要原因。动脉粥样硬化是大多数 CVD 的病因。动脉粥样硬化斑块的形成及随后的血栓形成是一个持续的过程，受到许多危险因素的影响，如高血压、糖尿病、血脂异常、肥胖、吸烟、炎症和久坐的生活方式。在各种风险和保护因素中，葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症的作用仍存在争议，这种酶缺乏症是人群中最常见的先天性酶缺陷。几十年来，它一直被认为是预防 CVD 发展的保护因素。然而，近年来，越来越多的科学证据表明，这种遗传条件可能是 CVD 的一个风险因素。G6PD 缺乏症在动脉粥样硬化形成过程中的作用已经通过体外或离体细胞模型、动物模型以及不同大小和不同种族人群的人类队列的流行病学研究进行了研究，但结果存在冲突。在这篇综述中，考虑到最近关于分子和生化机制的发现，即抗氧化机制、谷胱甘肽循环和一氧化氮产生，以及它们之间的相互作用，在戊糖磷酸途径中，由于酶缺陷，这些机制可能会受到损害，我们批判性地重新考虑了 G6PD 缺乏症对 CVD 的影响。总的来说，目前的证据支持这样一种观点，即 G6PD 下调可能有利于 CVD 高危人群动脉粥样硬化的发生和发展。鉴于这种酶在世界上几个地区的相对高发频率，这一发现可能对制定监测指南和促进风险分层具有实际意义。
