Angiotensin 2 AND Sirt3

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown...

Atherosclerosis (AS) is a major health problem and targeting the associated molecular pathways is critical for developing therapies. The present study investigated the effect of coptisine on human umbilical vein endothelial cells (HUVECs) in response to angiotensin II (Ang II) induction by focusing on cellular senescence, apoptosis and inflammation. HUVECs were treated with different Ang II concentrations and long non-coding RNA small nucleolar RNA host gene 12 (SNHG12), microRNA (miRNA/miR)-603 and nicotinamide phosphoribosyltransferase (NAMPT) expressions were assessed...

Hypertensive nephropathy is characterized by long-term damage to renal tissues by chronic uncontrolled hypertension, and ultimately leads to the development of renal fibrosis. The epithelial-mesenchymal transition (EMT) potentially contributes to the promotion of renal fibrosis in chronic kidney disease (CKD). In this study, we investigated the potential roles of canagliflozin (Cana) on renal EMT and oxidative stress through its effects on sirtuin 3 (SIRT3) expression. High-salt diet (HSD)-induced Dahl salt-sensitive rats hypertensive renal injury led to decreased SIRT3 expression and an increase in EMT and oxidative stress...

Doxorubicin (DOX) is an effective and widely used anticancer drug but has limited clinical applicability because of its cardiotoxicity. Ferroptosis plays a key role in DOX-induced cardiac damage and cardiomyocyte cell death. The inhibition of ferroptosis reverses DOX-induced cardiotoxicity (DIC). LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, protects against DIC. However, the mechanism of action of LCZ696, especially its effect on ferroptosis, is incompletely understood. This study investigates the cardioprotective effects of LCZ696 on DIC in vivo and in vitro...

Sirtuin 3 (SIRT3) is a major mitochondrial NAD-dependent Deacetylase closely involved in energy production, cell metabolism, oxidative stress responses, and mitochondrial homeostasis during hypertension and kidney diseases. However, it remains unknown whether deletion of SIRT3 in the proximal tubules alters the hypertensive and kidney glomerular and tubulointerstitial fibrotic responses to angiotensin II (Ang II) in sex-dependent manners. In the present study, adult male and female wild-type (WT) and mutant mice with proximal tubule-specific deletion of SIRT3, PT-Sirt3-/- , were infused without (time controls) or with a slow pressor dose of Ang II via an osmotic minipump (0...

Hypertension remains a major health problem in Western Societies, and blood pressure is poorly controlled in a third of patients despite use of multiple drugs. Mitochondrial dysfunction contributes to hypertension, and mitochondria-targeted agents can potentially improve treatment of hypertension. We have proposed that mitochondrial oxidative stress produces reactive dicarbonyl lipid peroxidation products, isolevuglandins, and that scavenging of mitochondrial isolevuglandins improves vascular function and reduces hypertension...

BACKGROUND: Cardiac hypertrophy is a prominent feature of heart remodeling, which may eventually lead to heart failure. Tongmaiyangxin (TMYX) pills are a clinically used botanical drug for treating multiple cardiovascular diseases including chronic heart failure. The aim of the current study was to identify the bioactive compounds in Tongmaiyangxin pills that attenuate cardiomyocytes hypertrophy, and to investigate the underlying mechanism of action. METHODS AND RESULTS: The anti-hypertrophy effect of TMYX was validated in isoproterenol-induced cardiac hypertrophy model in C57BL/6 mice...

Background : It has been reported that Angiotensin II (Ang II) induced skeletal muscle atrophy. However, the precise mechanisms remain elusive. Sirtuin 3 (SIRT3), an NAD-dependent deacetylase, plays a central role in maintaining cellular metabolic homeostasis. This work aims to determine the role of SIRT3-mediated cellular metabolism in skeletal muscle wasting. Methods and Results : Eight-week-old male wild-type (WT) and SIRT3 knockout (SIRT3 KO) mice were infused with Ang II or saline for 4 weeks. Ang II induces skeletal muscle atrophy by inducing expression of the muscle-enriched E3 ubiquitin ligase muscle RING-finger-1 (MuRF1) and atrogin-1, accompanied by a reduction in SIRT3 in skeletal muscle...

<b/> Background: The cellular and molecular mechanisms of cardioprotective effects of Vitamin D are poorly understood. Given the essential role of sirtuin-3 (SIRT3) as an endogenous negative regulator of cardiac hypertrophy, this study was designed to investigate the effect of 1, 25-dihydroxyvitamin D3 (calcitriol) on hypertrophy markers and SIRT3 mRNA and protein levels following angiotensin II induced - hypertrophy in cardiomyoblast H9c2 cells. Methods: Rat cardiomyoblast H9c2 cells were treated for 48 hr with angiotensin II alone (Ang group) or in combination with 1, 10 and 100 nM of calcitriol (C + Ang groups)...

Tobacco smoking is a major risk factor for cardiovascular disease and hypertension. It is associated with the oxidative stress and induces metabolic reprograming altering mitochondrial function. We hypothesized that cigarette smoke induces cardiovascular mitochondrial oxidative stress which contributes to endothelial dysfunction and hypertension. To test this hypothesis, we studied if scavenging of mitochondrial H2 O2 in transgenic mice expressing mitochondria-targeted catalase (mCAT) attenuates the development of cigarette smoke/angiotensin II-induced mitochondrial oxidative stress and hypertension compared with wild-type mice...

Microglia activation and its mediated production of proinflammatory mediators play important roles in different neurodegenerative diseases; hence, modulation of microglia activation has been considered a potential therapeutic strategy to ameliorate neurodegeneration. This study was aimed to determine whether Gastrodin, a common herbal agent known to possess neuroprotective property, can attenuate production of proinflammatory mediators in activated microglia through the renin-angiotensin system (RAS) and Sirtuin3 (SIRT3)...

BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin- 1beta (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia...

RATIONALE: Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years of age paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine dinucleotide, reduced form) and acetyl-CoA levels. Sirt3 impairment reduces the activity of a key mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2) because of hyperacetylation. OBJECTIVE: In this study, we examined whether the loss of Sirt3 activity increases vascular oxidative stress because of SOD2 hyperacetylation and promotes endothelial dysfunction and hypertension...

Silent mating type information regulation 2 homolog 3 (SIRT3) is a major protective mediator that ameliorates oxidative stress and mitochondrial dysfunction, which are associated with the pathogenesis of epithelial-mesenchymal transition (EMT). The present study was aimed to investigate the potential role of SIRT3 in renal tubular EMT both in vitro and in vivo. Firstly, we showed that the expression of SIRT3 was repressed in angiotensin II-induced EMT. SIRT3 deficiency triggered EMT response, while over-expression of SIRT3 attenuated EMT response...

Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H2 O2 -induced injury and hypoxia/reoxygenation-induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored...