Effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia

Shi, Wen; Shangguan, Wenfeng; Zhang, Yue; Li, Can; Li, Guangping

doi:10.14744/anatoljcardiol.2017.7771

Cited by 13 publications

(11 citation statements)

References 37 publications

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“…Mitochondrial fission and fusion regulate a number of cellular processes, including bioenergetic potency, mitochondrial apoptosis, autophagy, organelle distribution and morphogenetic processes [39]. Mitochondrial fusion/fission is primarily regulated by dynamin-like GTPase, optic atrophy 1 (Opa1) and dynamin-related protein 1 (Drp1, mitofusin 1/2 (Mfn1/2) [40][41][42]. Recently, it was reported that the mRNA expression level of Opa1 is reduced in sIBM [43].…”

Section: Plos Onementioning

confidence: 99%

Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

et al. 2020

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Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.

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Section: Plos Onementioning

confidence: 99%

Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

et al. 2020

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“…This might be an indication of oxidative stress and renal cell death following the administration of NaF. Previous studies have shown that NaF‐induced apoptosis via upregulation of p38 and downregulations of both p‐ERK and total ERK . Therefore, quercetin administration was able to quench oxidative and ameliorate apoptosis as observed in the lower expressions of p38.…”

Section: Discussionmentioning

confidence: 91%

Quercetin attenuates hypertension induced by sodium fluoride via reduction in oxidative stress and modulation of HSP 70/ERK/PPARγ signaling pathways

et al. 2018

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Hypertension is one of the silent killers in the world with high mortality and morbidity. The exposure of humans and animals to fluoride and/or fluoride containing compounds is almost inevitable. This study investigated the modulatory effects of quercetin on sodium fluoride (NaF)-induced hypertension and cardiovascular complications. Forty male rats were randomly separated into four groups (n =10). Group A animals served as the control, rats in Group B were exposed to 300 ppm of NaF, Groups C and D animals were exposed to 300 ppm of NaF along with quercetin orally at 50 mg/kg and 100 mg/kg orally by gavage, while NaF was administered in drinking water, respectively, for a week. Administration of NaF caused severe hypertension as indicated with significant increases in the systolic, diastolic, and mean arterial blood pressure, togetherAbbreviations: ANOVA, one-way analysis of variance; AOPP, advanced oxidation protein product; AP-1, activator protein-1; AST, aspartate aminotransfer-

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“…It prevents diabetic cardiomyopathy by inhibiting NOX2/TrPC3-induced oxidative stress [ 37 ], and protects against atherosclerosis by reducing reactive oxygen species production and regulating smooth muscle proliferation [ 38 ]. In addition, TMZ has also been implicated in the regulation of mitochondrial metabolism, mitochondrial biosynthesis, and mitochondrial fission/fusion [ 39 , 40 ]. In contrast to previous studies, our study confirms that TMZ attenuates cardiac hypertrophy and heart failure by improving angiogenesis dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Trimetazidine enhances myocardial angiogenesis in pressure overload-induced cardiac hypertrophy mice through directly activating Akt and promoting the binding of HSF1 to VEGF-A promoter

et al. 2022

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Latest clinical research shows that trimetazidine therapy during the perioperative period relieves endothelial dysfunction in patients with unstable angina induced by percutaneous coronary intervention. In this study we investigated the effects of TMZ on myocardial angiogenesis in pressure overload-induced cardiac hypertrophy mice. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC) surgery. TAC mice were administered trimetazidine (2.8 mg/100 µL, i.g.) for 28 consecutive days. We showed that trimetazidine administration significantly increased blood vessel density in the left ventricular myocardium and abrogated cardiac dysfunction in TAC mice. Co-administration of a specific HSF1 inhibitor KRIBB11 (1.25 mg/100 µL, i.h.) abrogated the angiogenesis-promoting effects of trimetazidine in TAC mice. Using luciferase reporter and electrophoretic mobility shift assays we demonstrated that the transcription factor HSF1 bound to the promoter region of VEGF-A, and the transcriptional activity of HSF1 was enhanced upon trimetazidine treatment. In molecular docking analysis we found that trimetazidine directly bound to Akt via a hydrogen bond with Asp292 and a pi–pi bond with Trp80. In norepinephrine-treated HUVECs, we showed that trimetazidine significantly increased the phosphorylation of Akt and the synergistic nuclear translocation of Akt and HSF1, as well as the binding of Akt and HSF1 in the nucleus. These results suggest that trimetazidine enhances myocardial angiogenesis through a direct interaction with Akt and promotion of nuclear translocation of HSF1, and that trimetazidine may be used for the treatment of myocardial angiogenic disorders in hypertensive patients.

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Effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia

Cited by 13 publications

References 37 publications

Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

Quercetin attenuates hypertension induced by sodium fluoride via reduction in oxidative stress and modulation of HSP 70/ERK/PPARγ signaling pathways

Trimetazidine enhances myocardial angiogenesis in pressure overload-induced cardiac hypertrophy mice through directly activating Akt and promoting the binding of HSF1 to VEGF-A promoter

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