Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy
            Via VEGFR-2 Signaling Pathway

Zhong, Wenliang; Wen, Ji; Xu, Shuai; Wu, Yanqing; Luo, Shunxiang; Liang, Minlie; Chen, Lianglong

doi:10.5935/abc.20180108

Cited by 7 publications

(12 citation statements)

References 34 publications

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“…In vitro and in vivo observations showed pioglitazone to have anti-hypertrophic potential in cultured mice cardiomyocytes via inhibition of vascular endothelial growth factor (VEGF) [ 48 ] and inhibition of pressure overload-induced increases in cardiac wall thickness and myocyte diameter in wild-type mice. Moreover, it reduced the increase in the heart weight-to-body weight ratio in heterozygous non-diabetic PPAR-γ-deficient mice [ 49 ], suggesting PPAR-γ independent activity.…”

Section: Effects Of Pioglitazone On the Heartmentioning

confidence: 99%

Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug

Nesti

Tricò

Mengozzi

et al. 2021

Cardiovasc Diabetol

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Since 1985, the thiazolidinedione pioglitazone has been widely used as an insulin sensitizer drug for type 2 diabetes mellitus (T2DM). Although fluid retention was early recognized as a safety concern, data from clinical trials have not provided conclusive evidence for a benefit or a harm on cardiac function, leaving the question unanswered. We reviewed the available evidence encompassing both in vitro and in vivo studies in tissues, isolated organs, animals and humans, including the evidence generated by major clinical trials. Despite the increased risk of hospitalization for heart failure due to fluid retention, pioglitazone is consistently associated with reduced risk of myocardial infarction and ischemic stroke both in primary and secondary prevention, without any proven direct harm on the myocardium. Moreover, it reduces atherosclerosis progression, in-stent restenosis after coronary stent implantation, progression rate from persistent to permanent atrial fibrillation, and reablation rate in diabetic patients with paroxysmal atrial fibrillation after catheter ablation. In fact, human and animal studies consistently report direct beneficial effects on cardiomyocytes electrophysiology, energetic metabolism, ischemia–reperfusion injury, cardiac remodeling, neurohormonal activation, pulmonary circulation and biventricular systo-diastolic functions. The mechanisms involved may rely either on anti-remodeling properties (endothelium protective, inflammation-modulating, anti-proliferative and anti-fibrotic properties) and/or on metabolic (adipose tissue metabolism, increased HDL cholesterol) and neurohormonal (renin–angiotensin–aldosterone system, sympathetic nervous system, and adiponectin) modulation of the cardiovascular system. With appropriate prescription and titration, pioglitazone remains a useful tool in the arsenal of the clinical diabetologist.

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Section: Effects Of Pioglitazone On the Heartmentioning

confidence: 99%

Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug

Nesti

Tricò

Mengozzi

et al. 2021

Cardiovasc Diabetol

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“…For pioglitazone, a study once reported that pioglitazone upregulated the levels of sphingomyelinase and ceramidase, a mediator of cardiomyocyte apoptosis (Baranowski et al, 2007). Moreover, by activating Bax and phosphorylated p53 as well as suppressing phosphorylated Akt and mTOR, pioglitazone could induce apoptosis in a VEGFR-2 dependent manner (Zhong et al, 2018).…”

Section: Antidiabetic Drugs (Rosiglitazone and Pioglitazone)mentioning

confidence: 99%

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Wei

Zhang

et al. 2020

Front. Cell Dev. Biol.

101

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Homeostatic regulation of cardiomyocytes plays a crucial role in maintaining the normal physiological activity of cardiac tissue. Severe cardiotoxicity results in cardiac diseases including but not limited to arrhythmia, myocardial infarction and myocardial hypertrophy. Drug-induced cardiotoxicity limits or forbids further use of the implicated drugs. Such drugs that are currently available in the clinic include anti-tumor drugs (doxorubicin, cisplatin, trastuzumab, etc.), antidiabetic drugs (rosiglitazone and pioglitazone), and an antiviral drug (zidovudine). This review focused on cardiomyocyte death forms and related mechanisms underlying clinical drug-induced cardiotoxicity, including apoptosis, autophagy, necrosis, necroptosis, pryoptosis, and ferroptosis. The key proteins involved in cardiomyocyte death signaling were discussed and evaluated, aiming to provide a theoretical basis and target for the prevention and treatment of drug-induced cardiotoxicity in the clinical practice.

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“…Pio, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, displays protective roles in cardiovascular diseases. 5) Recently, Pio is reported to play an important role in ischemic heart disease, such as heart failure 6) and myocardial infarction. 7) However, the exact mechanism of Pio on apoptosis of myocardial cells induced via I/R injury has been rarely studied.…”

mentioning

confidence: 99%

Pioglitazone Protects Against Hypoxia-Induced Cardiomyocyte Apoptosis Through Inhibiting NLRP3/Caspase-1 Pathway <i>in vivo</i> and <i>in vitro</i>

et al. 2022

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This study aims to explore the underlying mechanisms of how Pioglitazone (Pio) affects myocardial ischemia-reperfusion (I/R) injury. In this study, after pretreatment of Pio, the pathologic change of myocardial tissues was measured via hematoxylin and eosin staining. The release of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and nitric oxide (NO) were measured. The cardiomyocyte apoptosis was detected via TUNEL assay and flow cytometry assay. The mitochondrial membrane potential (ΔΨm) was estimated using the JC-1 probe. The release of cytochrome c in mitochondria and the translocation of cytochrome c in the cytosol were measured using western blot. Additionally, apoptosis-associated molecules and NOD-like receptor pyrin domain containing-3 (NLRP3)/caspase-1 pathway-related molecules were measured using western blot, quantitative real-time-polymerase chain reaction, and immunofluorescence staining. Results showed that the pretreatment of Pio significantly decreased myocardial tissue damage. Pio pretreatment inhibited the release of creatine kinase and LDH but promoted NO release in serum and H9c2 cell supernatants. Moreover, the pretreatment of Pio notably alleviated cardiomyocyte apoptosis. Pio pretreatment also maintained the mitochondrial membrane potential and prevented cytochrome c release in H/R-induced cardiomyocytes. Additionally, we confirmed that Pio pretreatment inhibited cardiomyocyte apoptosis via repressing the NLRP3/caspase-1 pathway. In conclusion, our study demonstrated that Pio could inhibit myocardial I/R injury and cardiomyocyte apoptosis by inhibiting the activation of the NLRP3/caspase-1 signaling pathway.

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Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway

Cited by 7 publications

References 34 publications

Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug

Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Pioglitazone Protects Against Hypoxia-Induced Cardiomyocyte Apoptosis Through Inhibiting NLRP3/Caspase-1 Pathway <i>in vivo</i> and <i>in vitro</i>

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