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Renin-Angiotensin System in Health and Diseases
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Renin-Angiotensin System in Health and Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 January 2026 | Viewed by 3862

Special Issue Editor

Dr. Keiko Hosohata

E-Mail Website
Guest Editor
Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki 569-1094, Japan
Interests: renal physiology; diabetic kidney disease; acute kidney injury; chronic kidney disease; proteinuria; hypertension; renal and renovascular hypertension; renal renin angiotensin system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Renin-angiotensin-aldosterone systems (RAAS) play critical roles in the regulation of blood pressure (BP), body fluid homeostasis, and cardiovascular function. Various tissues, including the heart and kidneys, possess individual locally regulated RAASs. Overactivity of the cardiac RAAS is associated with cardiac diseases, including cardiac hypertrophy due to volume and/or pressure overload, heart failure, coronary artery disease with myocardial infarction, and hypertension. The overactivity of the renal RAAS is associated with various kidney diseases such as nephropathies and renal artery stenosis. RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor AT(1) blockers (ARBs) is very useful for the treatment of arterial hypertension, chronic heart failure (CHF), chronic kidney disease (CKD), atherosclerosis, and diabetes. Then, attention has been paid to basic studies about new insights into molecular RAAS mechanisms in vitro and in vivo and clinical studies about RAAS blockers.

Recently, ACE2 is considered as a SARS-CoV-2 receptor and involved in the pathogenesis of coronavirus disease 2019 (COVID-19). ACE2 has important functions in the renin–angiotensin system (RAS): blood pressure maintenance and electrolyte homeostasis. Several reports found increases in ACE2 expression in the lung associated with numerous chronic comorbidities and as a function of increasing age, consistent with the risk for severe COVID-19. The influence of the RAAS on the progression of COVID-19 has been a topic of debate, and the full extent of RAAS involvement in the long-term consequences of COVID-19, such as long COVID and the cardiovascular thrombotic effects post-COVID, along with those following vaccination, remains not entirely resolved. The role of the RAAS in procoagulant processes during COVID-19 is of particular importance.

The purpose of this Special Issue is to present the current efforts in the involvement of the RAAS in the molecular mechanisms underpinning hypertension, CHD, and CKD, as well as procoagulant processes throughout COVID-19, from the viewpoint of pathogenesis of organ complications as well as clinical outcomes. Original research articles, review articles, and short communications within (but not limited to) the research areas described above are welcome.

Dr. Keiko Hosohata
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • coronavirus disease 2019 (COVID-19)
  • SARS-CoV-2
  • RAAS
  • spike protein
  • angiotensin
  • ACE2
  • clinical study
  • basic experiments

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Published Papers (2 papers)

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Review

23 pages, 1440 KiB  
Review
Direct Vascular Effects of Angiotensin II (A Systematic Short Review)
by György L. Nádasy, András Balla, Gabriella Dörnyei, László Hunyady and Mária Szekeres
Int. J. Mol. Sci. 2025, 26(1), 113; https://doi.org/10.3390/ijms26010113 - 26 Dec 2024
Cited by 1 | Viewed by 2488
Abstract
The octapeptide angiotensin II (Ang II) is a circulating hormone as well as a locally formed agonist synthesized by the angiotensin-converting enzyme (ACE) of endothelial cells. It forms a powerful mechanism to control the amount and pressure of body fluids. All main effects [...] Read more.
The octapeptide angiotensin II (Ang II) is a circulating hormone as well as a locally formed agonist synthesized by the angiotensin-converting enzyme (ACE) of endothelial cells. It forms a powerful mechanism to control the amount and pressure of body fluids. All main effects are directed to save body salt and water and ensure blood pressure under basic conditions and in emergencies. All blood vessels respond to stimulation by Ang II; the immediate response is smooth muscle contraction, increasing vascular resistance, and elevating blood pressure. Such effects are conveyed by type 1 angiotensin receptors (AT1Rs) located in the plasma membrane of both endothelial and vascular smooth muscle cells. AT1Rs are heterotrimeric G protein-coupled receptors (GPCRs), but their signal pathways are much more complicated than other GPCRs. In addition to Gq/11, the G12/13, JAK/STAT, Jnk, MAPK, and ERK 1/2, and arrestin-dependent and -independent pathways are activated because of the promiscuous attachment of different signal proteins to the intracellular G protein binding site and to the intracellular C terminal loop. Substantial changes in protein expression follow, including the intracellular inflammation signal protein NF-κB, endothelial contact proteins, cytokines, matrix metalloproteinases (MMPs), and type I protocollagen, eliciting the inflammatory transformation of endothelial and vascular smooth muscle cells and fibrosis. Ang II is an important contributor to vascular pathologies in hypertensive, atherosclerotic, and aneurysmal vascular wall remodeling. Such direct vascular effects are reviewed. In addition to reducing blood pressure, AT1R antagonists and ACE inhibitors have a beneficial effect on the vascular wall by inhibiting pathological wall remodeling. Full article
(This article belongs to the Special Issue Renin-Angiotensin System in Health and Diseases)
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16 pages, 1132 KiB  
Review
Angiotensin-(1-7) and Central Control of Cardiometabolic Outcomes: Implications for Obesity Hypertension
by Victoria L. Vernail, Lillia Lucas, Amanda J. Miller and Amy C. Arnold
Int. J. Mol. Sci. 2024, 25(24), 13320; https://doi.org/10.3390/ijms252413320 - 12 Dec 2024
Cited by 1 | Viewed by 931
Abstract
Hypertension is a leading independent risk factor for the development of cardiovascular disease, the leading cause of death globally. Importantly, the prevalence of hypertension is positively correlated with obesity, with obesity-related hypertension being difficult to treat due to a lack of current guidelines [...] Read more.
Hypertension is a leading independent risk factor for the development of cardiovascular disease, the leading cause of death globally. Importantly, the prevalence of hypertension is positively correlated with obesity, with obesity-related hypertension being difficult to treat due to a lack of current guidelines in this population as well as limited efficacy and adverse off-target effects of currently available antihypertensive therapeutics. This highlights the need to better understand the mechanisms linking hypertension with obesity to develop optimal therapeutic approaches. In this regard, the renin–angiotensin system, which is dysregulated in both hypertension and obesity, is a prime therapeutic target. While research and therapies have typically focused on the deleterious angiotensin II axis of the renin–angiotensin system, emerging evidence shows that targeting the protective angiotensin-(1-7) axis also improves cardiovascular and metabolic functions in animal models of obesity hypertension. While the precise mechanisms involved remain under investigation, in addition to peripheral actions, evidence exists to support a role for the central nervous system in the beneficial cardiometabolic effects of angiotensin-(1-7). This review will highlight emerging translational studies exploring the cardiovascular and metabolic regulatory actions of angiotensin-(1-7), with an emphasis on its central actions in brain regions including the brainstem and hypothalamus. An improved understanding of the central mechanisms engaged by angiotensin-(1-7) to regulate cardiovascular and metabolic functions may provide insight into the potential of targeting this hormone as a novel therapeutic approach for obesity-related hypertension. Full article
(This article belongs to the Special Issue Renin-Angiotensin System in Health and Diseases)
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