International Journal of Molecular Sciences

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Special Issue Editor

Dr. Sean P. Didion

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Guest Editor

1. Department of Pharmacology, The University of Mississippi Medical Center, Jackson, MS 39216, USA
2. Department of Neurology, The University of Mississippi Medical Center, Jackson, MS 39216, USA
Interests: inflammation; superoxide; vascular biology; NADPH oxidase; angiotensin II; endothelial nitric oxide synthase

Special Issue Information

Dear Colleagues,

Classically, the renin–angiotensin system (RAS) plays an important role in cardiovascular homeostasis. Insights gained from research into the RAS in the last two decades have revealed that several components of the RAS, most notably angiotensin II and angiotensin-converting enzymes (ACEs), serve to promote inflammatory pathways in several diseases, including hypertension, as well as mediating SARS-CoV-2 infection. Angiotensin II, the main effector molecule of the (RAS), has been linked to increases in inflammatory cytokines, such as interleukin-6, thereby promoting and/or enhancing end-organ injury. In addition to its classical role in the enzymatic cleavage of angiotensin I to angiotensin II, ACEs also serve as the biological receptor for SARS-CoV-2. As the role that the RAS plays in disease processes has expanded, especially during the COVID-19 pandemic, the aim of this Special Issue is to enhance our knowledge and understanding of the role the RAS plays in immune signaling, cardiovascular disease, as well as SARS-CoV-2 infection. This topic is especially timely as we begin to enter the post-COVID-19 pandemic era.

Dr. Sean P. Didion
Guest Editor

Manuscript Submission Information

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Keywords

angiotensin II
angiotensin-converting enzyme
cytokines
cardiovascular disease
immune pathways
inflammation
inflammatory signaling
infection
renin–angiotensin system
SARS-CoV-2

Published Papers (2 papers)

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Review

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12 pages, 1273 KiB

Open AccessReview

Investigating the Impact of Selective Modulators on the Renin–Angiotensin–Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents

by Te-Ling Lu and Sheng-Nan Wu

Int. J. Mol. Sci. 2023, 24(18), 14007; https://doi.org/10.3390/ijms241814007 - 12 Sep 2023

Viewed by 1342

Abstract

The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in maintaining various physiological processes in the body, including blood pressure regulation, electrolyte balance, and overall cardiovascular health. However, any compounds or drugs known to perturb the RAAS might have an additional impact on transmembrane ionic currents. In this retrospective review article, we aimed to present a selection of chemical compounds or medications that have long been recognized as interfering with the RAAS. It is noteworthy that these substances may also exhibit regulatory effects in different types of ionic currents. Apocynin, known to attenuate the angiotensin II-induced activation of epithelial Na⁺ channels, was shown to stimulate peak and late components of voltage-gated Na⁺ current (I_Na). Esaxerenone, an antagonist of the mineralocorticoid receptor, can exert an inhibitory effect on peak and late I_Na directly. Dexamethasone, a synthetic glucocorticoid, can directly enhance the open probability of large-conductance Ca²⁺-activated K⁺ channels. Sparsentan, a dual-acting antagonist of the angiotensin II receptor and endothelin type A receptors, was found to suppress the amplitude of peak and late I_Na effectively. However, telmisartan, a blocker of the angiotensin II receptor, was effective in stimulating the peak and late I_Na along with a slowing of the inactivation time course of the current. However, telmisartan’s presence can also suppress the erg-mediated K⁺ current. Moreover, tolvaptan, recognized as an aquaretic agent that can block the vasopressin receptor, was noted to suppress the amplitude of the delayed-rectifier K⁺ current and the M-type K⁺ current directly. The above results indicate that these substances not only have an interference effect on the RAAS but also exert regulatory effects on different types of ionic currents. Therefore, to determine their mechanisms of action, it is necessary to gain a deeper understanding. Full article

(This article belongs to the Special Issue New Insights into the Role of the Renin–Angiotensin System in Disease)

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Other

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7 pages, 1472 KiB

Open AccessCase Report

Improved Graft Function following Desensitization of Anti-AT₁R and Autoantibodies in a Heart Transplant Recipient Negative for Donor-Specific Antibodies with Antibody-Mediated Rejection: A Case Report

by Regina Jung, Kevin Ly, Michiko Taniguchi, Aileen Grace Arriola, Christopher Gravante, Derek Shinn, Leena Mathew, Eman Hamad, Steven Geier and Abdelhamid Liacini

Int. J. Mol. Sci. 2024, 25(4), 2218; https://doi.org/10.3390/ijms25042218 - 12 Feb 2024

Viewed by 743

Abstract

HLA donor-specific antibodies (DSAs) pre and post transplant increase the risk of antibody-mediated rejection (AMR) and lead to poor graft survival. Increasing data exist to support the involvement of non-HLA antibodies in triggering an immunological response. The development of non-HLA antibodies specific for AT₁R is associated with poor clinical outcomes in orthotopic heart transplant recipients. This case presents an investigation of non-HLA antibodies in a 56-year-old female heart transplant recipient diagnosed with AMR in the absence of DSAs. Full article

(This article belongs to the Special Issue New Insights into the Role of the Renin–Angiotensin System in Disease)

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