Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019

Author:

Swiderski Jordan1ORCID,Gadanec Laura Kate1ORCID,Apostolopoulos Vasso12ORCID,Moore Graham J.34,Kelaidonis Konstantinos5,Matsoukas John M.1456ORCID,Zulli Anthony1

Affiliation:

1. Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia

2. Immunology Program, Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia

3. Pepmetics Incorporated, 772 Murphy Place, Victoria, BC V8Y 3H4, Canada

4. Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada

5. NewDrug PC, Patras Science Park, 26500 Patras, Greece

6. Department of Chemistry, University of Patras, 26504 Patras, Greece

Abstract

Cardiovascular diseases (CVDs) are the main contributors to global morbidity and mortality. Major pathogenic phenotypes of CVDs include the development of endothelial dysfunction, oxidative stress, and hyper-inflammatory responses. These phenotypes have been found to overlap with the pathophysiological complications of coronavirus disease 2019 (COVID-19). CVDs have been identified as major risk factors for severe and fatal COVID-19 states. The renin–angiotensin system (RAS) is an important regulatory system in cardiovascular homeostasis. However, its dysregulation is observed in CVDs, where upregulation of angiotensin type 1 receptor (AT1R) signaling via angiotensin II (AngII) leads to the AngII-dependent pathogenic development of CVDs. Additionally, the interaction between the spike protein of severe acute respiratory syndrome coronavirus 2 with angiotensin-converting enzyme 2 leads to the downregulation of the latter, resulting in the dysregulation of the RAS. This dysregulation favors AngII/AT1R toxic signaling pathways, providing a mechanical link between cardiovascular pathology and COVID-19. Therefore, inhibiting AngII/AT1R signaling through angiotensin receptor blockers (ARBs) has been indicated as a promising therapeutic approach to the treatment of COVID-19. Herein, we review the role of AngII in CVDs and its upregulation in COVID-19. We also provide a future direction for the potential implication of a novel class of ARBs called bisartans, which are speculated to contain multifunctional targeting towards COVID-19.

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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