Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease

Abstract

Angiotensin-converting enzyme/angiotensin II/type 1 angiotensin receptors (ACE/AngII/AT1) axis of the renninangiotensin system plays an integral role in maintaining vascular tone, salt and water homeostasis, as well as cardiac function in humans. Chronic activation of AngII/AT1 causes hypertension accompanied by cardiac, renal, and vascular injury with remodeling that eventually leads to end-organ damage, such as renal failure, heart failure, and coronary artery disease. 1 During the last decade, classical view of the renninangiotensin system has been challenged by the discovery of ACE2. This membrane-bound enzyme has been identified in rodents and humans, and is found mainly in the heart and kidney. 2 The major role of ACE2 is to cleave AngII to generate Ang1-7. The biological effects of Ang1-7 in the kidney are primarily mediated by interaction with the G-proteincoupled receptor Mas. However, other complex effects have been described that may involve receptor-receptor interactions with AT1 or type 2 angiotensin receptors (AT2) receptors, as well as nuclear receptor binding. 3 The ACE2/Ang1-7/Mas axis counterbalances the role of ACE/ AngII/AT1 axis, thus imparting broader influences on the cardiovascular system, including vasodilatation, myocardial protection, antiarrhythmic effects, and inhibition of pathological cardiac remodeling. 4 Furthermore, a number of experimental findings suggest that Ang1-7 also plays a protective role in the kidney. 5,6 Hypertensive kidney disease is a clinical condition that causes damage to the kidney because of chronic high blood pressure. The renal pathological changes are gradual and progressive, characterized by glomerular damage, followed by glomerular sclerosis and interstitial fibrosis. 7 The intensity of fibrosis correlates with the degree of glomerular filtration deficit. Multiple factors, including Ang1-7, have been shown to contribute to the renal pathological changes. Ang1-7 is reported to attenuate fibrosis in liver, skeletal muscle, and heart. 8 A growing body of evidence supports a role for endogenous or exogenous Ang1-7 serving as a protectant

Cordyceps cicadae Ameliorates Renal Hypertensive Injury and Fibrosis Through the Regulation of SIRT1-Mediated Autophagy

“…On the other hand, peroxidation levels, such those as of H 2 O 2 and AngII, in abnormal conditions may induce apoptosis via silent information regulator 2 homolog 1 (SIRT1) and other signaling pathways ( Lakhani et al, 2019 ; Park et al, 2020 ; Wu et al, 2020 ; Huang et al, 2021 ). Malondialdehyde (MDA) is a major byproduct in oxidative stress that affects kidney fibrogenesis related to hypertension ( Chen et al, 2019 ). Superoxide dismutase (SOD) is an important antioxidant enzyme that plays an indispensable role in free-radical scavenging and blocking the progression of HN ( da Silva Cristino Cordeiro et al, 2018 ).…”

BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model

“…Fibrillar collagen accumulation (fibrosis) by collagen-specific Picrosirius Red staining as evaluated as previously reported [ 51 , 52 ]. Collagen volume fraction in the kidney was quantitated as previously reported and calculated as the percentage of connective tissue (red) areas compared to the sum of connective tissue area and non-connective tissue in all fields of the kidney section (20 sections/kidney).…”

Cardiovascular Disease Complicating COVID-19 in the Elderly

“…ACE2, homologous to ACE, cleavages AngII via an alternative pathway to form Angiotensin 1–7. Angiotensin 1–7 has vasodilatory effects and protect against acute respiratory distress syndrome (ARDS) [ 70 ]. ACE2 is constitutively expressed in the lungs, kidney, gastrointestinal tract, and endothelium.…”