-
Hypertension (Dallas, Tex. : 1979) May 2024The renin-angiotensin system is the most important peptide hormone system in the regulation of cardiovascular homeostasis. Its classical arm consists of the enzymes,... (Review)
Review
The renin-angiotensin system is the most important peptide hormone system in the regulation of cardiovascular homeostasis. Its classical arm consists of the enzymes, renin, and angiotensin-converting enzyme, generating angiotensin II from angiotensinogen, which activates its AT receptor, thereby increasing blood pressure, retaining salt and water, and inducing cardiovascular hypertrophy and fibrosis. However, angiotensin II can also activate a second receptor, the AT receptor. Moreover, the removal of the C-terminal phenylalanine from angiotensin II by ACE2 (angiotensin-converting enzyme 2) yields angiotensin-(1-7), and this peptide interacts with its receptor Mas. When the aminoterminal Asp of angiotensin-(1-7) is decarboxylated, alamandine is generated, which activates the Mas-related G-protein-coupled receptor D, MrgD (Mas-related G-protein-coupled receptor type D). Since Mas, MrgD, and the AT receptor have opposing effects to the classical AT receptor, they and the enzymes and peptides activating them are called the alternative or protective arm of the renin-angiotensin system. This review will cover the historical aspects and the current standing of this recent addition to the biology of the renin-angiotensin system.
Topics: Angiotensin I; Angiotensin II; Peptide Fragments; Peptides; Peptidyl-Dipeptidase A; Receptors, G-Protein-Coupled; Renin; Renin-Angiotensin System; Humans
PubMed: 38362781
DOI: 10.1161/HYPERTENSIONAHA.123.21364 -
Frontiers in Immunology 2023Sarcoidosis is a systemic inflammatory disease of unknown etiology, which mainly affects the lungs and lymph nodes, as well as extrapulmonary organs. Its incidence, and... (Review)
Review
Sarcoidosis is a systemic inflammatory disease of unknown etiology, which mainly affects the lungs and lymph nodes, as well as extrapulmonary organs. Its incidence, and prevalence rate, and disease course largely vary with regions and populations globally. The clinical manifestations of sarcoidosis depend on the affected organs and the degree of severity, and the diagnosis is mainly based on serum biomarkers, radiographic, magnetic resonance, or positron emission tomography imaging, and pathological biopsy. Noncaseating granulomas composing T cells, macrophages, epithelioid cells, and giant cells, were observed in a pathological biopsy, which was the characteristic pathological manifestation of sarcoidosis. Angiotensin-converting enzyme (ACE) was first found in the renin-angiotensin-aldosterone system. Its main function is to convert angiotensin I (Ang I) into Ang II, which plays an important role in regulating blood pressure. Also, an ACE insertion/deletion polymorphism exists in the human genome, which is involved in the occurrence and development of many diseases, including hypertension, heart failure, and sarcoidosis. The serum ACE level, most commonly used as a biomarker in diagnosing sarcoidosis, in patients with sarcoidosis increases. because of epithelioid cells and giant cells of sarcoid granuloma expressing ACE. Thus, it serves as the most commonly used biomarker in the diagnosis of sarcoidosis and also aids in analyzing its therapeutic effect and prognosis in patients with sarcoidosis.
Topics: Humans; Biomarkers; Granuloma; Lymph Nodes; Renin-Angiotensin System; Sarcoidosis; Peptidyl-Dipeptidase A
PubMed: 37868968
DOI: 10.3389/fimmu.2023.950095 -
Critical Care (London, England) Nov 2023The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and the cardio-renal system. The classical RAS, mainly mediated by angiotensin I,... (Review)
Review
The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and the cardio-renal system. The classical RAS, mainly mediated by angiotensin I, angiotensin-converting enzyme, and angiotensin II, has been reported to be altered in critically ill patients, such as those in vasodilatory shock. However, recent research has highlighted the role of some components of the counterregulatory axis of the classical RAS, termed the alternative RAS, such as angiotensin-converting Enzyme 2 (ACE2) and angiotensin-(1-7), or peptidases which can modulate the RAS like dipeptidyl-peptidase 3, in many critical situations. In cases of shock, dipeptidyl-peptidase 3, an enzyme involved in the degradation of angiotensin and opioid peptides, has been associated with acute kidney injury and mortality and preclinical studies have tested its neutralization. Angiotensin-(1-7) has been shown to prevent septic shock development and improve outcomes in experimental models of sepsis. In the context of experimental acute lung injury, ACE2 activity has demonstrated a protective role, and its inactivation has been associated with worsened lung function, leading to the use of active recombinant human ACE2, in preclinical and human studies. Angiotensin-(1-7) has been tested in experimental models of acute lung injury and in a recent randomized controlled trial for patients with COVID-19 related hypoxemia. Overall, the alternative RAS appears to have a role in the pathogenesis of disease in critically ill patients, and modulation of the alternative RAS may improve outcomes. Here, we review the available evidence regarding the methods of analysis of the RAS, pathophysiological disturbances of this system, and discuss how therapeutic manipulation may improve outcomes in the critically ill.
Topics: Humans; Renin-Angiotensin System; Angiotensin-Converting Enzyme 2; Critical Illness; Angiotensin II; Acute Lung Injury
PubMed: 37986086
DOI: 10.1186/s13054-023-04739-5 -
Genes Oct 2023The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to...
The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to oxidative stress, contributing to its beneficial effects on overall health. The aim of this study was to assess the effects of MedD treatment in healthy human volunteers on the expression of ten genes related to oxidative stress and inflammation in women and men. Of 30 enrolled subjects, 17 were eligible, 10 women and 7 men. All of them received the same MedD treatment. Before and after 8 weeks of MedD treatment, an evaluation of body composition, blood tests, and anthropometric and clinical parameters was performed. Furthermore, 10 genes were amplified and analyzed. The study showed significant differences between females and males in body composition and biochemical parameters before and after MedD treatment. Significant differences between females and males in Resistance Force ( < 0.009) and Diastolic Blood Pressure ( < 0.04) before MedD treatment, and in High-Density Lipoprotein ( < 0.02) after MedD treatment, were observed. Moreover, a significant upregulation of and in females has been shown. Sex differences impact MedD treatment response, and influence the genetic expression of genes related to oxidative stress; our findings may help to personalize diet therapy and contribute to overall health and well-being.
Topics: Humans; Male; Female; Diet, Mediterranean; Pilot Projects; Nutrigenomics; Sex Characteristics; Oxidative Stress
PubMed: 38002923
DOI: 10.3390/genes14111980