Swiderski, Jordan ORCID: 0000-0002-3613-2406, Gadanec, Laura Kate ORCID: 0000-0002-4801-8061, Apostolopoulos, Vasso ORCID: 0000-0001-6788-2771, Moore, Graham J, Kelaidonis, Konstantinos, Matsoukas, John ORCID: 0000-0001-5554-2964 and Zulli, Anthony ORCID: 0000-0002-2660-078X (2023) Role of angiotensin II in cardiovascular diseases: introducing bisartans as a novel therapy for Coronavirus 2019. Biomolecules, 13 (5). ISSN 2218-273X

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.

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