Role of the Renin-Angiotensin System in Long COVID’s Cardiovascular Injuries

Abstract

The renin-angiotensin system (RAS) is one of the biggest challenges of cardiovascular medicine. The significance of the RAS in the chronic progression of SARS-CoV-2 infection and its consequences is one of the topics that are currently being mostly discussed. SARS-CoV-2 undermines the balance between beneficial and harmful RAS pathways. The level of soluble ACE2 and membrane-bound ACE2 are both upregulated by the endocytosis of the SARS-CoV-2/ACE2 complex and the tumor necrosis factor (TNF)-α-converting enzyme (ADAM17)-induced cleavage. Through the link between RAS and the processes of proliferation, the processes of fibrous remodelling of the myocardium are initiated from the acute phase of the disease, continuing into the long COVID stage. In the long term, RAS dysfunction may cause an impairment of its beneficial effects leading to thromboembolic processes and a reduction in perfusion of target organs. The main aspects of ACE2—a key pathogenic role in COVID-19 as well as the mechanisms of RAS involvement in COVID cardiovascular injuries are studied. Therapeutic directions that can be currently anticipated in relation to the various pathogenic pathways of progression of cardiovascular damage in patients with longCOVID have also been outlined.

Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review

“…ACE2 has multifaceted functions: its extracellular spike protein binding domain designates it as the entry receptor for coronaviruses, its monocarboxypeptidase activity maintains physiological homeostasis and safeguards various organ systems, and its collectrin-like domain functions as a neutral amino acid transporter. While recent scientific research refutes the initial notion of using ACE2 inhibitors to prevent the binding between the coronavirus and ACE2, further insights suggest that upregulating and/or activating ACE2 can prevent the cytokine storm induced by COVID-19 . In this review, we noted that the complexity of the mechanisms governing ACE2 upregulation, with only a few identified ACE2 transcription factors and epigenetic modulators.…”

“…While recent scientific research refutes the initial notion of using ACE2 inhibitors to prevent the binding between the coronavirus and ACE2, further insights suggest that upregulating and/or activating ACE2 can prevent the cytokine storm induced by COVID-19. 155 In this review, we noted that the complexity of the mechanisms governing ACE2 upregulation, with only a few identified ACE2 transcription factors and epigenetic modulators. In contrast, ACE2 activation results from a singular mechanism that targets its hinge-bending region.…”

Exploring post-SEPSIS and post-COVID-19 syndromes: crossovers from pathophysiology to therapeutic approach

“…When bound with SARS-CoV-2 with ACE2 the normal conversion of Ang II to Ang (1-7) becomes inhibited, increasing Ang II activity. Addition of a synthetic Ang (1-7), TXA-127, achieves RAS balance (44). Other RAS inhibitors need to be further investigated as a great opportunity to have effective treatment in PASC.…”

From Living in Saltwater to a Scarcity of Salt and Water, and Then an Overabundance of Salt—The Biological Roller Coaster to Which the Renin–Angiotensin System Has Had to Adapt: An Editorial

“…The elements of RAS will be involved in several subsequent pathological events. Such long post-COVID cardiovascular injuries have been reviewed by Cojocaru et al in a recent Special Issue [9].…”