Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

Ji, Xiaobing; Li, Xiurong; Hao-Ding,; Sun, Qi; Zhou, Yang; Wen, Ping; Dai, Chunsun; Yang, Junwei

doi:10.1159/000430142

Cited by 18 publications

(11 citation statements)

References 30 publications

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“…ATP levels were calculated as μM and expressed on the basis of wet tissue weight. A kit based on luciferin/luciferase assay has also been recently used by other researchers for determination of ATP levels [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Malfitano

Souza

Carbonaro

et al. 2015

Cardiovasc Diabetol

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BackgroundThe effects of streptozotocin (STZ)-induced diabetes on heart metabolism and function after myocardial infarction (MI) remodelling were investigated in rats.MethodsFifteen days after STZ (50 mg/kg b.w. i.v.) injection, MI was induced by surgical occlusion of the left coronary artery. Two weeks after MI induction, contents of glycogen, ATP, free fatty acids and triacylglycerols (TG) and enzyme activities of glycolysis and Krebs cycle (hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase, citrate synthase) and expression of carnitine palmitoyl-CoA transferase I (a key enzyme of mitochondrial fatty acid oxidation) were measured in the left ventricle (LV). Plasma glucose, free fatty acids and triacylglycerol levels were determined. Ejection fraction (EF) and shortening fraction (SF) were also measured by echocardiography.ResultsGlycogen and TG contents were increased (p < 0.05) whereas ATP content was decreased in the LV of the non-infarcted diabetic group when compared to the control group (p < 0.05). When compared to infarcted control rats (MI), the diabetic infarcted rats (DI) showed (p < 0.05): increased plasma glucose and TG levels, elevated free fatty acid levels and increased activity of, citrate synthase and decreased ATP levels in the LV. Infarct size was smaller in the DI group when compared to MI rats (p < 0.05), and this was associated with higher EF and SF (p < 0.05).ConclusionsSystolic function was preserved or recovered more efficiently in the heart from diabetic rats two weeks after MI, possibly due to the high provision of glucose and free fatty acids from both plasma and heart glycogen and triacylglycerol stores.

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Section: Methodsmentioning

confidence: 99%

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Malfitano

Souza

Carbonaro

et al. 2015

Cardiovasc Diabetol

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“…In animal model of heart failure induced by pressure overload induced by constriction of the ascending aorta, the expression of UCP2 and UCP3 is downregulated and an increase of ROS generation is enhanced to induce cardiac cell hypertrophy [38, 44]. However this model does not involve FFAs-induced upregulation of UCPs that may protect cell from hypertrophy and dysfunction.…”

Section: General Characteristics Of Ucpsmentioning

confidence: 99%

Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

Ruiz-Ramírez

López-Acosta

Barrios-Maya

et al. 2016

Oxidative Medicine and Cellular Longevity

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Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS) generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs), specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection.

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“…In the mammalian heart, UCP2 is the predominant isoform that expressed in the heart and other tissues . It has been reported that UCP2 plays an important role in myocardial injury and cardiac hypertrophy . Nevertheless, the exact role and mechanism of UCP2 in cardioprotection during I/R remain elusive.…”

Section: Introductionmentioning

confidence: 99%

UCP2 protect the heart from myocardial ischemia/reperfusion injury via induction of mitochondrial autophagy

Liu

et al. 2019

J of Cellular Biochemistry

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Uncoupling protein 2 (UCP2), located in the mitochondrial inner membrane, is a predominant isoform of UCP that expressed in the heart and other tissues of human and rodent tissues. Nevertheless, its functional role during myocardial ischemia/reperfusion (I/R) is not entirely understood. Ischemic preconditioning (IPC) remarkably improved postischemic functional recovery followed by reduced lactate dehydrogenase (LDH) release with simultaneous upregulation of UCP2 in perfused myocardium. We then investigated the role of UCP2 in IPC‐afforded cardioprotective effects on myocardial I/R injury with adenovirus‐mediated in vivo UCP2 overexpression (AdUCP2) and knockdown (AdshUCP2). IPC‐induced protective effects were mimicked by UCP2 overexpression, while which were abolished with silencing UCP2. Mechanistically, UCP2 overexpression significantly reinforced I/R‐induced mitochondrial autophagy (mitophagy), as measured by biochemical hallmarks of mitochondrial autophagy. Moreover, primary cardiomyocytes infected with AdUCP2 increased simulated ischemia/reperfusion (sI/R)‐induced mitophagy and therefore reversed impaired mitochondrial function. Finally, suppression of mitophagy with mdivi‐1 in cultured cardiomyocytes abolished UCP2‐afforded protective effect on sI/R‐induced mitochondrial dysfunction and cell death. Our data identify a critical role for UCP2 against myocardial I/R injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.

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Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

Cited by 18 publications

References 30 publications

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

UCP2 protect the heart from myocardial ischemia/reperfusion injury via induction of mitochondrial autophagy

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