Role of the calcium sensing receptor in cardiomyocyte apoptosis via mitochondrial dynamics in compensatory hypertrophied myocardium of spontaneously hypertensive rat

Hong, Siting; Zhang, Xin; Zhang, Xiaohui; Liu, Wenxiu; Fu, Yu; Liu, Yue; Shi, Zhiyu; Chi, Jinyu; Zhao, Meng; Yin, Xinhua

doi:10.1016/j.bbrc.2017.04.126

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…In vivo studies have shown that even if ROS levels do not increase significantly, mtDNA damage can reduce mitochondrial respiration and ATP content in smooth muscle cells, promote apoptosis of VSMCs and aggravate atherosclerosis ( Yu et al, 2014 ). After endothelial injury, proliferation, migration, and vascular remodeling of VSMCs are important for the rupture of atherosclerotic plaques, wherein the fission of mitochondria and deregulated secondary morphological functions play an important role ( Wang et al, 2015 ; Hong et al, 2017 ). Once mitochondrion fission is inhibited by silencing Drp1, the protons leak across the mitochondrial inner membrane, resulting in decreased ROS levels in primary mouse smooth muscle cells, a phenomenon that inhibits smooth muscle cell migration ( Wang et al, 2015 ; Figure 2E ).…”

Section: Novel Mechanistic Insights: From Mitochondrial Dynamics To Atherosclerosismentioning

confidence: 99%

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Yang

Xing

et al. 2021

Front. Cell Dev. Biol.

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Cardiovascular disease (CVD) is the main cause of death worldwide. Atherosclerosis is the underlying pathological basis of CVD. Mitochondrial homeostasis is maintained through the dynamic processes of fusion and fission. Mitochondria are involved in many cellular processes, such as steroid biosynthesis, calcium homeostasis, immune cell activation, redox signaling, apoptosis, and inflammation, among others. Under stress conditions, mitochondrial dynamics, mitochondrial cristae remodeling, and mitochondrial ROS (mitoROS) production increase, mitochondrial membrane potential (MMP) decreases, calcium homeostasis is imbalanced, and mitochondrial permeability transition pore open (mPTP) and release of mitochondrial DNA (mtDNA) are activated. mtDNA recognized by TLR9 can lead to NF-κB pathway activation and pro-inflammatory factor expression. At the same time, TLR9 can also activate NLRP3 inflammasomes and release interleukin, an event that eventually leads to tissue damage and inflammatory responses. In addition, mitochondrial dysfunction may amplify the activation of NLRP3 through the production of mitochondrial ROS, which together aggravate accumulating mitochondrial damage. In addition, mtDNA defects or gene mutation can lead to mitochondrial oxidative stress. Finally, obesity, diabetes, hypertension and aging are risk factors for the progression of CVD, which are closely related to mitochondrial dynamics. Mitochondrial dynamics may represent a new target in the treatment of atherosclerosis. Antioxidants, mitochondrial inhibitors, and various new therapies to correct mitochondrial dysfunction represent a few directions for future research on therapeutic intervention and amelioration of atherosclerosis.

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Section: Novel Mechanistic Insights: From Mitochondrial Dynamics To Atherosclerosismentioning

confidence: 99%

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Yang

Xing

et al. 2021

Front. Cell Dev. Biol.

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“…CaSR gets involved in myocardial hypertrophy and apoptosis through activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) signaling pathways in an isoproterenol induced cardiac injury model [ 12 ]. CaSR causes cardiac hypertrophy through activating autophagy and promoting the release of Ca 2+ from sarcoplasmic reticulum to mitochondria in the rat heart failure model, and aggravates cardiac apoptosis through activating mitochondrial dynamics-mediated apoptotic pathway in rat hypertensive hearts model [ 13 , 14 ]. CaN is one of serine/threonine protein phosphatases, which is activated mainly by the continuous increase of Ca 2+ .…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway

Lü

Wang²,

Sun

et al. 2021

Journal of Ginseng Research

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Background Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca 2+ ] i , and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca 2+ ] i , which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-β1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl 3 could not further increase the [Ca 2+ ] i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca 2+ ] i and CaN signaling but had no effect on CaSR expression. Conclusion The activation of CaN pathway and the increase of [Ca 2+ ] i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

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“…Other treatments against the adverse effects induced by HTN have been reported beyond direct manipulation of Drp1 or calcium sensing receptors ( 118 – 121 ). Poly(ADP-ribose) polymerase-inhibition prevented the development of LV hypertrophy in spontaneously hypertensive rats (SHR) through inactivation of Drp1 and activation of Opa1 and Mfn2 ( 122 ).…”

Section: Mitochondrial Dynamics In Vascular Diseasesmentioning

confidence: 99%

“…Compared to wild type, SHR hearts exhibit significant upregulation of Drp1, whereas Opa1 and Mfn2 are downregulated. Calhex 231 , an inhibitor of calcium sensing receptor, ameliorates these mitochondrial dynamics changes, resulting in inhibition of apoptosis in hypertensive hearts ( 121 ). Interestingly, alpha1 receptor agonists affect mitochondrial fusion as well as fission, resulting in LV hypertrophy.…”

Section: Mitochondrial Dynamics In Vascular Diseasesmentioning

confidence: 99%

Current Understanding of the Pivotal Role of Mitochondrial Dynamics in Cardiovascular Diseases and Senescence

Uchikado

Ikeda

Ohishi

2022

Front. Cardiovasc. Med.

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The heart is dependent on ATP production in mitochondria, which is closely associated with cardiovascular disease because of the oxidative stress produced by mitochondria. Mitochondria are highly dynamic organelles that constantly change their morphology to elongated (fusion) or small and spherical (fission). These mitochondrial dynamics are regulated by various small GTPases, Drp1, Fis1, Mitofusin, and Opa1. Mitochondrial fission and fusion are essential to maintain a balance between mitochondrial biogenesis and mitochondrial turnover. Recent studies have demonstrated that mitochondrial dynamics play a crucial role in the development of cardiovascular diseases and senescence. Disruptions in mitochondrial dynamics affect mitochondrial dysfunction and cardiomyocyte survival leading to cardiac ischemia/reperfusion injury, cardiomyopathy, and heart failure. Mitochondrial dynamics and reactive oxygen species production have been associated with endothelial dysfunction, which in turn causes the development of atherosclerosis, hypertension, and even pulmonary hypertension, including pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Here, we review the association between cardiovascular diseases and mitochondrial dynamics, which may represent a potential therapeutic target.

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Role of the calcium sensing receptor in cardiomyocyte apoptosis via mitochondrial dynamics in compensatory hypertrophied myocardium of spontaneously hypertensive rat

Cited by 12 publications

References 29 publications

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway

Current Understanding of the Pivotal Role of Mitochondrial Dynamics in Cardiovascular Diseases and Senescence

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