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Special Issue Editors

Prof. Dr. Rosario Scalia

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Guest Editor

Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA

Dr. Tatsuo Kawai

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Guest Editor

Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA
Interests: I have a strong interest in understanding cardiovascular diseases and metabolic disorders such as diabetes mellitus and dyslipidemia; I have been conducting research to clarify the pathogenic mechanisms of vascular and organ damage, and I am interested in developing novel strategies for prevention and treatment of these damages

Special Issue Information

Dear Colleagues,

The renin angiotensin aldosterone system (RAAS) plays a crucial role in cardiovascular physiology and pathophysiology, by regulating vascular constriction, fluid volume regulation, cell growth, and so on. Angiotensin II (Ang II), the major bioactive peptide of the RAAS, is one of the key players in RAAS, mediating various signal transduction cascades by activating its receptors, such as Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R). The importance of functional crosstalk between the AngII-AT1R signalling pathway and the other signalling pathways has also been elucidated. Furthermore, accumulating evidence has revealed the role of systemic and local RAAS in cardiovascular diseases (CVDs) in clinical settings, and RAAS is a widely recognized therapeutic target in patients with CVDs. Over the past three decades, many basic and clinical research studies have unveiled the complex role of RAAS in CVDs. However, many questions still remain to be elucidated. Therefore, this Special Issue on “The Role of Angiotensin in Cardiovascular Disease” will include, but is not limited to, the articles investigating the molecular mechanisms of the RAAS in CVDs, translational evaluations on these findings, and in vitro, in vivo and clinical studies examining how the RAAS is involved in cardiovascular and metabolic disorders. This Special Issue also welcomes review articles summarizing up-to-date overviews of recent angiotensin signalling and its functional significance in CVDs.

Prof. Dr. Rosario Scalia
Dr. Tatsuo Kawai
Guest Editors

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Keywords

Angiotensin II
RAAS
Cardiovascular diseases
AT1

Published Papers (2 papers)

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Research

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13 pages, 2343 KiB

Open AccessEditor’s ChoiceArticle

Receptor Interactions of Angiotensin II and Angiotensin Receptor Blockers—Relevance to COVID-19

by Graham J. Moore, Jose M. Pires, Konstantinos Kelaidonis, Laura Kate Gadanec, Anthony Zulli, Vasso Apostolopoulos and John M. Matsoukas

Biomolecules 2021, 11(7), 979; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11070979 - 03 Jul 2021

Cited by 15 | Viewed by 2841

Abstract

Angiotensin II (Ang II) may contain a charge relay system (CRS) involving Tyr/His/carboxylate, which creates a tyrosinate anion for receptor activation. Energy calculations were carried out to determine the preferred geometry for the CRS in the presence and absence of the Arg guanidino group occupying position 2 of Ang II. These findings suggest that Tyr is preferred over His for bearing the negative charge and that the CRS is stabilized by the guanidino group. Recent crystallography studies provided details of the binding of nonpeptide angiotensin receptor blockers (ARBs) to the Ang II type 1 (AT1) receptor, and these insights were applied to Ang II. A model of binding and receptor activation that explains the surmountable and insurmountable effects of Ang II analogues sarmesin and sarilesin, respectively, was developed and enabled the discovery of a new generation of ARBs called bisartans. Finally, we determined the ability of the bisartan BV6(TFA) to act as a potential ARB, demonstrating similar effects to candesartan, by reducing vasoconstriction of rabbit iliac arteries in response to cumulative doses of Ang II. Recent clinical studies have shown that Ang II receptor blockers have protective effects in hypertensive patients infected with SARS-CoV-2. Therefore, the usage of ARBS to block the AT1 receptor preventing the binding of toxic angiotensin implicated in the storm of cytokines in SARS-CoV-2 is a target treatment and opens new avenues for disease therapy. Full article

(This article belongs to the Special Issue The Role of Angiotensin in Cardiovascular Disease)

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Review

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20 pages, 1556 KiB

Open AccessEditor’s ChoiceReview

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

by Jordan Swiderski, Laura Kate Gadanec, Vasso Apostolopoulos, Graham J. Moore, Konstantinos Kelaidonis, John M. Matsoukas and Anthony Zulli

Biomolecules 2023, 13(5), 787; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13050787 - 02 May 2023

Cited by 3 | Viewed by 4055

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. Full article

(This article belongs to the Special Issue The Role of Angiotensin in Cardiovascular Disease)

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