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Review
. 2021 Dec 15;17(5):53-62.
doi: 10.14797/mdcvj.1044. eCollection 2021.

Acute and Chronic Cardiovascular Manifestations of COVID-19: Role for Endotheliopathy

John P Cooke  1 , John H Connor  2 , Abhishek Jain  3   4
Affiliations
Review

Acute and Chronic Cardiovascular Manifestations of COVID-19: Role for Endotheliopathy

John P Cooke et al. Methodist Debakey Cardiovasc J. .

Abstract

SARS-CoV-2, the virus that causes coronavirus disease 19 (COVID-19), is associated with a bewildering array of cardiovascular manifestations, including myocardial infarction and stroke, myocarditis and heart failure, atrial and ventricular arrhythmias, venous thromboembolism, and microvascular disease. Accumulating evidence indicates that a profound disturbance of endothelial homeostasis contributes to these conditions. Furthermore, the pulmonary infiltration and edema, and later pulmonary fibrosis, in patients with COVID-19 is promoted by endothelial alterations including the expression of endothelial adhesion molecules and chemokines, increased intercellular permeability, and endothelial-to-mesenchyme transitions. The cognitive disturbance occurring in this disease may also be due in part to an impairment of the blood-brain barrier. Venous thrombosis and pulmonary thromboembolism are most likely associated with an endothelial defect caused by circulating inflammatory cytokines and/or direct endothelial invasion by the virus. Endothelial-targeted therapies such as statins, nitric oxide donors, and antioxidants may be useful therapeutic adjuncts in COVID-19 by restoring endothelial homeostasis.

Keywords: SARS-CoV-2; cerebrovascular attack; deep venous thrombosis; dementia; endothelium; myocardial infarction; myocarditis; nitric oxide; pulmonary embolism.

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Figures

SARS-CoV-2 activates inflammatory signaling within endothelial cells (EC) that alters endothelial homeostasis and promotes inflammation, vascular permeability, and thrombosis
Figure 1
SARS-CoV-2 activates inflammatory signaling within endothelial cells (EC) that alters endothelial homeostasis and promotes inflammation, vascular permeability, and thrombosis. Epigenetic alterations contribute to the acute and chronic manifestations of COVID endotheliopathy. NOS: nitric oxide synthase; NO: nitric oxide; WBCs: white blood cells; RBCs: red blood cells; PAMP: pathogen-associated molecular patterns; DAMP: damage-associated molecular patterns; CVD: cardiovascular disease.
Infographic describing how the vein-chip will model endotheliopathy and thrombosis in COVID-19
Figure 2
Infographic describing how the vein-chip will model endotheliopathy and thrombosis in COVID-19. Bottom fluorescence micrograph and scanning electron image taken from Rajeeva et al. Microengineered Human Vein-Chip Recreates Venous Valve Architecture and Its Contribution to Thrombosis. Small. 2020;16(49):2003401. doi: 10.1002/smll.202003401
A section of vein-chip
Figure 3
A section of vein-chip. Human vein-chip more accurately models human venous architecture, flow, and thrombosis. Taken from Rajeeva et al. Microengineered Human Vein-Chip Recreates Venous Valve Architecture and Its Contribution to Thrombosis. Small. 2020;16:2003401. doi: 10.1002/smll.202003401. Image enlarged using Let’s Enhance.
Pathways in endothelial cells (ECs) that contribute to epigenetic alterations and EC loss of function causing downstream cardiovascular disease
Figure 4
Pathways in endothelial cells (ECs) that contribute to epigenetic alterations and EC loss of function causing downstream cardiovascular disease. ACE2: angiotensin converting enzyme 2; DM: diabetes mellitus; TOB: tobacco exposure; DAMP: damage-associated molecular patterns; HC: hypercholesterolemia PRR: pattern recognition receptors; JAK/STAT: Janus kinase signal transducer and activator of transcription; NF-kB: nuclear factor kappa B; IRF-7: interferon regulatory factor 7; CAVD: calcific aortic valve disease; CRF: corticotropin-releasing factor; HFPEF: heart failure with preserved ejection fraction; PAH/RVP: pulmonary arterial hypertension/right ventricular pressure; CAD/MI: coronary artery disease/myocardial infarction; CAV: cardiac allograft vasculopathy; PAD: peripheral arterial disease; HTN: hypertension.
See this image and copyright information in PMC

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