The atlas of ACE2 expression in fetal and adult human hearts reveals the potential mechanism of heart-injured patients infected with SARS-CoV-2

Shao, Xiuli; Zhang, Xiaolin; Zhang, Ruijia; Zhu, Rongli; Hou, Xiuyang; Yi, Weijue; Wu, Fang; Liang, Hao; Feng, Rui

doi:10.1152/ajpcell.00169.2021

Cited by 5 publications

(2 citation statements)

References 62 publications

(65 reference statements)

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“…In all such studies, ACE2 was minimally detected in vascular ECs, suggesting that direct infection of the endothelium is not a major pathogenic mechanism for the microvascular damage observed in COVID-19 tissue specimens. 38,[93][94][95] Instead, strong expression of ACE2 was detected in pericytes, 38,[93][94][95] fibroblast-like vascular mural cells that wrap around ECs of the microvasculature and regulate their function. The intimate interaction between pericytes and microvascular ECs substantiates the likelihood that direct SARS-CoV-2 infection of pericytes accounts for the microvascular EC damage commonly found in tissue specimens of COVID-19 nonsurvivors.…”

Section: Sars-cov-2 Infectivity Of the Heartmentioning

confidence: 99%

Cell-Specific Mechanisms in the Heart of COVID-19 Patients

Tsai

Čiháková

Tucker

2023

Circulation Research

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From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type–specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type–specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.

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Section: Sars-cov-2 Infectivity Of the Heartmentioning

confidence: 99%

Cell-Specific Mechanisms in the Heart of COVID-19 Patients

Tsai

Čiháková

Tucker

2023

Circulation Research

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“…In human cardiomyocytes, ACE2 is expressed in atria and ventricles, smooth muscle cells, fibroblasts, and endothelial cells [ 171 ]. In addition to the action of ACE2, Ang (1-7) can be produced in the heart from Ang I (1-10) by propyl endopeptidase and neural endopeptidase (NEP) [ 129 ].…”

Section: Reviewmentioning

confidence: 99%

Renin-Angiotensin System: Updated Understanding and Role in Physiological and Pathophysiological States

Kanugula¹,

Kaur²,

Batra³

et al. 2023

Cureus

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The classical view of the renin-angiotensin system (RAS) is that of the circulating hormone pathway involved in salt and water homeostasis and blood pressure regulation. It is also involved in the pathogenesis of cardiac and renal disorders. This led to the creation of drugs blocking the actions of this classical pathway, which improved cardiac and renal outcomes. Our understanding of the RAS has significantly expanded with the discovery of new peptides involved in this complex pathway. Over the last two decades, a counterregulatory or protective pathway has been discovered that opposes the effects of the classical pathway. Components of RAS are also implicated in the pathogenesis of obesity and its metabolic diseases. The continued discovery of newer molecules also provides novel therapeutic targets to improve disease outcomes. This article aims to provide an overview of an updated understanding of the RAS, its role in physiological and pathological processes, and potential novel therapeutic options from RAS for managing cardiorenal disorders, obesity, and related metabolic disorders.

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