Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway

Cao, Shiping; Zeng, Ziyue; Wang, Xiaochang C.; Bin, Jianping; Xu, Dingli; Liao, Yulin

doi:10.3892/mmr.2013.1622

Cited by 12 publications

(5 citation statements)

References 33 publications

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“…The mitochondrial matrix protease CLPP plays a central role in the activation of the UPRmt, 10.3389/fcvm.2022.945142 deletion of CLPP in heart increased the synthesis of oxidative phosphorylation subunits and attenuated the mitochondrial cardiomyopathy (91). Cao et al showed that parvostatin improved left ventricular function and slowed the progression of heart failure in mice by blocking UPRmt activator c-Jun (92). The contradictory effects of UPRmt on heart may due to its intensive degree.…”

Section: Dysregulation Of Mitochondrial Proteostasis In Heart Failurementioning

confidence: 99%

Mitochondrial dysfunction in heart failure and its therapeutic implications

Liu

Pan

et al. 2022

Front. Cardiovasc. Med.

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The ATP consumption in heart is very intensive to support muscle contraction and relaxation. Mitochondrion is the power plant of the cell. Mitochondrial dysfunction has long been believed as the primary mechanism responsible for the inability of energy generation and utilization in heart failure. In addition, emerging evidence has demonstrated that mitochondrial dysfunction also contributes to calcium dysregulation, oxidative stress, proteotoxic insults and cardiomyocyte death. These elements interact with each other to form a vicious circle in failing heart. The role of mitochondrial dysfunction in the pathogenesis of heart failure has attracted increasing attention. The complex signaling of mitochondrial quality control provides multiple targets for maintaining mitochondrial function. Design of therapeutic strategies targeting mitochondrial dysfunction holds promise for the prevention and treatment of heart failure.

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Section: Dysregulation Of Mitochondrial Proteostasis In Heart Failurementioning

confidence: 99%

Mitochondrial dysfunction in heart failure and its therapeutic implications

Liu

Pan

et al. 2022

Front. Cardiovasc. Med.

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“…For example, atorvastatin could attenuate myocardial hypertrophy and remodeling in spontaneously hypertensive rats by inhibiting apoptosis and reversing mitochondrial metabolism via C/EBPβ/ PGC-1α/UCP3 signaling pathway [43]. Moreover, pravastatin attenuated cardiac remodeling via inhibiting JNKdependent pro-apoptotic signaling [44].…”

Section: Lowering Serum Lipids Improves Heart Functionmentioning

confidence: 99%

Mechanisms underlying direct actions of hyperlipidemia on myocardium: an updated review

2020

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Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of non-ischemic heart failure, while decreasing serum lipids can reverse heart dysfunction. Apart from indirectly affecting the function of the heart by promoting the development of atherosclerosis, hyperlipidemia also affects the systolic function and cardiac electrophysiological response of the heart directly, which may be related to gradual accumulation of cardiac lipids and consequent systemic oxidative stress, proinflammatory state and mitochondrial dysfunction. However, the mechanism underlying direct effects of hyperlipidemia on the heart are not fully understood. In this review, we provide an updated summary of recent experimental and clinical studies that focus on elucidating the mechanisms of the action of hyperlipidemia on cardiac function, the relationship between heart failure and serum lipids, and protective effects of lipid-lowering drugs on the heart. The exciting progress in this field supports the prospect of guiding early protection of the heart to benefit the patients with chronic hyperlipidemia and familial hyperlipidemia.

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“…Abundant evidence supports an important role for MAPK in mediating cell apoptosis through the activation of apoptosis-related genes (30)(31)(32)(33)(34)(35). More importantly, it was reported that MAPK activation is mediated by sublytic C5b-9 stimulation (36,37).…”

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confidence: 99%

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2–p38 MAPK–IRF-1–TRADD–Caspase 8 in Rat Thy-1 Nephritis

Zhu

Qiu

et al. 2017

The Journal of Immunology

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The apoptosis of glomerular mesangial cells (GMCs) in the early phase of rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis (MsPGN), is primarily triggered by sublytic C5b-9. However, the mechanism of GMC apoptosis induced by sublytic C5b-9 remains unclear. In this study, we demonstrate that expressions of TNFR1-associated death domain-containing protein (TRADD) and IFN regulatory factor-1 (IRF-1) were simultaneously upregulated in the renal tissue of Thy-1N rats (in vivo) and in GMCs under sublytic C5b-9 stimulation (in vitro). In vitro, TRADD was confirmed to be a downstream gene of IRF-1, because IRF-1 could bind to TRADD gene promoter to promote its transcription, leading to caspase 8 activation and GMC apoptosis. Increased phosphorylation of p38 MAPK was verified to contribute to IRF-1 and TRADD production and caspase 8 activation, as well as to GMC apoptosis induced by sublytic C5b-9. Furthermore, phosphorylation of MEK kinase 2 (MEKK2) mediated p38 MAPK activation. More importantly, three sites (Ser) of MEKK2 phosphorylation were identified and demonstrated to be necessary for p38 MAPK activation. In addition, silencing of renal MEKK2, IRF-1, and TRADD genes or inhibition of p38 MAPK activation in vivo had obvious inhibitory effects on GMC apoptosis, secondary proliferation, and urinary protein secretion in rats with Thy-1N. Collectively, these findings indicate that the cascade axis of MEKK2-p38 MAPK-IRF-1-TRADD-caspase 8 may play an important role in GMC apoptosis following exposure to sublytic C5b-9 in rat Thy-1N.

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Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway

Cited by 12 publications

References 33 publications

Mitochondrial dysfunction in heart failure and its therapeutic implications

Mitochondrial dysfunction in heart failure and its therapeutic implications

Mechanisms underlying direct actions of hyperlipidemia on myocardium: an updated review

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2–p38 MAPK–IRF-1–TRADD–Caspase 8 in Rat Thy-1 Nephritis

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