Recently, accumulating evidence has highlighted the role of endothelial dysfunction in COVID-19 progression. Coronary microvascular dysfunction (CMD) plays a pivotal role in cardiovascular disease (CVD) and CVD-related risk factors (eg, age, gender, hypertension, diabetes mellitus, and obesity). Equally, these are also risk factors for COVID-19. The purpose of this review was to explore CMD pathophysiology in COVID-19, based on recent evidence. COVID-19 mechanisms were reviewed in terms of imbalanced renin-angiotensin-aldosterone-systems (RAAS), systemic inflammation and immune responses, endothelial dysfunction, and coagulatory disorders. Based on these mechanisms, we addressed CMD pathophysiology within the context of COVID-19, from five perspectives. The first was the disarrangement of local RAAS and Kallikrein-kinin-systems attributable to SARS-Cov-2 entry, and the concomitant decrease in coronary microvascular endothelial angiotensin I converting enzyme 2 (ACE2) levels. The second was related to coronary microvascular obstruction, induced by COVID-19-associated systemic hyper-inflammation and pro-thrombotic state. The third was focused on how pneumonia/acute respiratory distress syndrome (ARDS)-related systemic hypoxia elicited oxidative stress in coronary microvessels and cardiac sympathetic nerve activation. Fourthly, we discussed how autonomic nerve dysfunction mediated by COVID-19-associated mental, physical, or physiological factors could elicit changes in coronary blood flow, resulting in CMD in COVID-19 patients. Finally, we analyzed reciprocity between the coronary microvascular endothelium and perivascular cellular structures due to viremia, SARS-CoV-2 dissemination, and systemic inflammation. These mechanisms may function either consecutively or intermittently, finally culminating in CMD-mediated cardiovascular symptoms in COVID-19 patients. However, the underlying molecular pathogenesis remains to be clarified.

中文翻译：

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COVID-19 冠状动脉微血管功能障碍的病理生理学


最近，越来越多的证据强调了内皮功能障碍在 COVID-19 进展中的作用。冠状动脉微血管功能障碍（CMD）在心血管疾病（CVD）和CVD相关危险因素（例如年龄、性别、高血压、糖尿病和肥胖）中发挥着关键作用。同样，这些也是 COVID-19 的危险因素。本综述的目的是根据最新证据探讨 COVID-19 中的 CMD 病理生理学。从肾素-血管紧张素-醛固酮系统（RAAS）失衡、全身炎症和免疫反应、内皮功能障碍和凝血障碍等方面对 COVID-19 机制进行了综述。基于这些机制，我们从五个角度探讨了 COVID-19 背景下的 CMD 病理生理学。第一个是由于 SARS-Cov-2 进入导致局部 RAAS 和激肽释放酶激肽系统紊乱，以及冠状动脉微血管内皮血管紧张素 I 转换酶 2 (ACE2) 水平随之下降。第二个与冠状微血管阻塞有关，这是由 COVID-19 相关的全身过度炎症和促血栓状态引起的。第三个重点是肺炎/急性呼吸窘迫综合征（ARDS）相关的全身缺氧如何引起冠状微血管的氧化应激和心脏交感神经激活。第四，我们讨论了由 COVID-19 相关的精神、身体或生理因素介导的自主神经功能障碍如何引起冠状动脉血流的变化，从而导致 COVID-19 患者出现 CMD。最后，我们分析了病毒血症、SARS-CoV-2 传播和全身炎症导致的冠状微血管内皮和血管周围细胞结构之间的相互作用。 这些机制可能连续或间歇性发挥作用，最终导致 COVID-19 患者出现 CMD 介导的心血管症状。然而，潜在的分子发病机制仍有待阐明。