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Journal of the American College of... Aug 2021
Topics: Angiotensin Receptor Antagonists; Angiotensins; Heart Failure; Humans
PubMed: 34325846
DOI: 10.1016/j.jacc.2021.04.100 -
The Journal of Biological Chemistry Oct 2020Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase involved in degrading oligopeptides with 4-12 amino acid residues. It has been associated with several...
Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase involved in degrading oligopeptides with 4-12 amino acid residues. It has been associated with several pathophysiological processes, including blood pressure regulation, pain signaling, and cancer cell defense against oxidative stress. However, the physiological substrates and the cellular pathways that are potentially targeted by DPP3 to mediate these effects remain unknown. Here, we show that global DPP3 deficiency in mice (DPP3) affects the renin-angiotensin system (RAS). LC-MS-based profiling of circulating angiotensin peptides revealed elevated levels of angiotensin II, III, IV, and 1-5 in DPP3 mice, whereas blood pressure, renin activity, and aldosterone levels remained unchanged. Activity assays using the purified enzyme confirmed that angiotensin peptides are substrates for DPP3. Aberrant angiotensin signaling was associated with substantially higher water intake and increased renal reactive oxygen species formation in the kidneys of DPP3 mice. The metabolic changes and altered angiotensin levels observed in male DPP3 mice were either absent or attenuated in female DPP3 mice, indicating sex-specific differences. Taken together, our observations suggest that DPP3 regulates the RAS pathway and water homeostasis by degrading circulating angiotensin peptides.
Topics: Angiotensins; Animals; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Female; Kidney; Male; Mice; Mice, Knockout; Reactive Oxygen Species; Renin-Angiotensin System; Sex Characteristics; Signal Transduction; Water-Electrolyte Balance
PubMed: 32546481
DOI: 10.1074/jbc.RA120.014183 -
Advances in Pharmacology (San Diego,... 2010The contribution of the renin angiotensin system to physiology and pathology is undergoing a rapid reconsideration of its mechanisms from emerging new concepts...
The contribution of the renin angiotensin system to physiology and pathology is undergoing a rapid reconsideration of its mechanisms from emerging new concepts implicating angiotensin-converting enzyme 2 and angiotensin-(1-7) as new elements negatively influencing the vasoconstrictor, trophic, and pro-inflammatory actions of angiotensin II. This component of the system acts to oppose the vasoconstrictor and proliferative effects on angiotensin II through signaling mechanisms mediated by the mas receptor. In addition, a reduced expression of the vasodepressor axis composed by angiotensin-converting enzyme 2 and angiotensin-(1-7) may contribute to the expression of essential hypertension, the remodeling of heart and renal function associated with this disease, and even the physiology of pregnancy and the development of eclampsia.
Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Antihypertensive Agents; Blood Pressure; Cardiovascular System; Female; Humans; Kidney; Male; Mice; Organ Specificity; Peptide Fragments; Peptidyl-Dipeptidase A; Pre-Eclampsia; Pregnancy; Rats; Receptors, Angiotensin; Renin-Angiotensin System
PubMed: 20933203
DOI: 10.1016/S1054-3589(10)59007-0 -
British Medical Journal Sep 1964
Topics: Angiotensins; Humans; Renin
PubMed: 14171057
DOI: 10.1136/bmj.2.5409.583 -
Kidney International. Supplement Apr 2000A number of kidney diseases, and their progression to end-stage renal disease, are driven, in part, by the effects of angiotensin II. Increasing levels of angiotensin II... (Review)
Review
A number of kidney diseases, and their progression to end-stage renal disease, are driven, in part, by the effects of angiotensin II. Increasing levels of angiotensin II may in turn up-regulate the expression of growth factors and cytokines, such as transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), osteopontin, vascular cell adhesion molecule-1 (VCAM-1), nuclear factor-kappaB (NF-kappaB), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor. Most of these compounds promote cell growth and fibrosis. Angiotensin II also stimulates oxidative stress. This stress in turn may potentiate the vasoconstrictor effect of the peptide due, in part, to increased catabolism of nitric oxide (NO). Oxidative stress, fueled in part by angiotensin II, up-regulates the expression of adhesion molecules, chemoattractant compounds and cytokines. The angiotensinogen gene, which provides the precursor for angiotensin production, is stimulated by NF-kappaB activation. NF-kappaB is activated by angiotensin in the liver and in the kidney. This provides an autocrine reinforcing loop that up-regulates angiotensin production. Angiotensin II activates NF-kappaB through both AT1 and AT2 receptors. In addition, angiotensin-converting enzyme (ACE) inhibition markedly decreases NF-kappaB activation in the setting of renal disease.
Topics: Angiotensins; Disease Progression; Growth Substances; Humans; Kidney Diseases; NF-kappa B; Tumor Necrosis Factor-alpha
PubMed: 10828755
DOI: No ID Found -
Biochemical Pharmacology Apr 2024The angiotensin AT2 receptor (ATR), an important member of the "protective arm" of the renin-angiotensin system (RAS), has been recently defined as a therapeutic target... (Review)
Review
The angiotensin AT2 receptor (ATR), an important member of the "protective arm" of the renin-angiotensin system (RAS), has been recently defined as a therapeutic target in different pathological conditions. The ATR activates complex signalling pathways linked to cellular proliferation, differentiation, anti-inflammation, antifibrosis, and induction or inhibition of apoptosis. The anti-inflammatory effect of ATR activation is commonly associated with reduced fibrosis in different models. Current discoveries demonstrated a direct impact of ATRs on the regulation of cytokines, transforming growth factor beta1 (TGF-beta1), matrix metalloproteases (MMPs), and synthesis of the extracellular matrix components. This review article summarizes current knowledge on the ATR in regard to immunity, inflammation and fibrosis in the heart and blood vessels. In particular, the differential influence of the ATR on cardiovascular remodeling in preclinical models of myocardial infarction, heart failure and aneurysm formation are discussed. Overall, these studies demonstrate that ATR stimulation represents a promising therapeutic approach to counteract myocardial and aortic damage in cardiovascular diseases.
Topics: Humans; Renin-Angiotensin System; Myocardial Infarction; Inflammation; Receptor, Angiotensin, Type 2; Myocardium; Angiotensins; Fibrosis; Receptor, Angiotensin, Type 1
PubMed: 38369211
DOI: 10.1016/j.bcp.2024.116062 -
Biochemical Pharmacology May 2024
Review
Topics: Receptors, Angiotensin; Renin-Angiotensin System; Renin; Angiotensins; Angiotensin II
PubMed: 38565339
DOI: 10.1016/j.bcp.2024.116180 -
The Journal of Frailty & Aging 2020It is unclear if angiotensin blocking drugs (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) reduce or increase the risk of falls and...
It is unclear if angiotensin blocking drugs (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) reduce or increase the risk of falls and fractures. We retrospectively analysed routinely-collected, linked health and social care data for patients aged 65 and over from Tayside, Scotland, including hospital discharge diagnoses, biochemistry, deaths, care package provision and community prescribing. We conducted unadjusted and adjusted Cox regression analyses for time to hip fracture and time to death, for any exposure to angiotensin blocking drugs and for time-dependent exposure to angiotensin blocking drugs. We analysed data on 16782 patients. Angiotensin blocking drug use was associated with an exposure-dependent lower risk of hip fracture (hazard ratio 0.988 [95%CI 0.982-0.994] per year of exposure; p<0.001) and death (hazard ratio 0.986 [95%CI 0.983-0.989] per year of exposure; p<0.001). These findings call into question the appropriateness of stopping angiotensin blocking drugs for older people at risk of falls.
Topics: Accidental Falls; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Hip Fractures; Humans; Mortality; Retrospective Studies; Risk Assessment
PubMed: 32259185
DOI: 10.14283/jfa.2019.38 -
Journal of Hypertension Jun 2020
Topics: Angiotensins; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Hypertension; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32371812
DOI: 10.1097/HJH.0000000000002468 -
Journal of Hypertension Jun 2020
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Betacoronavirus; COVID-19; Coronavirus; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32371811
DOI: 10.1097/HJH.0000000000002469