Cardioprotective Role of SIRT5 in Response to Acute Ischemia Through a Novel Liver-Cardiac Crosstalk Mechanism

Protein posttranslational modifications play important roles in cardiovascular diseases. The authors’ previous report showed that the abundance of succinylated and glutarylated proteins was significantly lower in the serum of patients with acute myocardial infarction (AMI) than in that of healthy volunteers, suggesting a potential relationship between protein acylation and AMI. Sirtuin 5 (SIRT5) facilitates the removal of malonyl, succinyl, and glutaryl modification; however, its effects on AMI remain unknown. In this study, the levels of SIRT5 in AMI mouse model was compared. Results showed elevated hepatic SIRT5 after myocardial infarction. Hepatocyte-specific SIRT5 overexpressing mice (liver SIRT5 OE) were generated to address the possible involvement of hepatic SIRT5 in AMI. The areas of myocardial infarction, myocardial fibrosis, and cardiac function in a model of experimental myocardial infarction were compared between liver SIRT5 OE mice and wild-type (WT) mice. The liver SIRT5 OE mice showed a significantly smaller area of myocardial infarction and myocardial fibrosis than the WT mice. The fibroblast growth factor 21 (FGF21) in the blood and myocardium of liver SIRT5 OE mice after AMI was markedly elevated compared with that in WT mice. The results of mass spectrometry showed increased levels of proteins regulating tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid β-oxidation pathways in the liver mitochondria of liver SIRT5 OE mice. These findings showed that SIRT5 may exhibit a cardioprotective effect in response to acute ischemia through a liver-cardiac crosstalk mechanism, probably by increasing the secretion of FGF21 and the improvement of energy metabolism.

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Role of delayed intraaortic balloon pumping in treatment of experimental myocardial infarction

The American Journal of Cardiology ◽

10.1016/0002-9149(78)90876-7 ◽

1978 ◽

Vol 41 (7) ◽

pp. 1202-1208 ◽

Cited By ~ 18

Author(s):

Arthur J. Roberts ◽

Daniel R. Alonso ◽

John R. Combes ◽

Jerome G. Jacobstein ◽

Martin R. Post ◽

...

Keyword(s):

Myocardial Infarction ◽

Experimental Myocardial Infarction ◽

Intraaortic Balloon ◽

Intraaortic Balloon Pumping

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Cardioprotective Role of Saxagliptin through Antioxidant Mechanism in Experimental Myocardial Infarction in STZ Induced Diabetic Rats

Clinical and Experimental Pharmacology ◽

10.4172/2161-1459.1000233 ◽

2017 ◽

Vol 07 (02) ◽

Cited By ~ 1

Author(s):

Mandlem VKK ◽

Annapurna A

Keyword(s):

Myocardial Infarction ◽

Diabetic Rats ◽

Experimental Myocardial Infarction ◽

Antioxidant Mechanism

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Protective Role of ADAMTS13 for Myocardium in Mouse Model of Experimental Myocardial Infarction.

Blood ◽

10.1182/blood.v120.21.2175.2175 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2175-2175

Author(s):

Masaaki Doi ◽

Hideto Matsui ◽

Yukiji Takeda ◽

Yoshihiko Saito ◽

Maiko Takeda ◽

...

Keyword(s):

Myocardial Infarction ◽

Ischemic Stroke ◽

Mouse Model ◽

Protective Role ◽

Experimental Myocardial Infarction ◽

Thrombotic Occlusion ◽

Cardiac Functions ◽

Functional Regulation ◽

Brain Ischemic Stroke

Abstract Abstract 2175 The metalloprotease ADAMTS13 regulates the size of von Willebrand factor (VWF) multimers, controlling excessive VWF functions and preventing thrombotic occlusion of microvasculature. We previously reported that ADAMTS13 deficiency aggravated the extent of brain ischemic stroke in a mouse model of middle cerebral arterial occlusion, suggesting the relevant role of ADAMTS13 in the pathophysiology of brain stroke (Fujioka, et al. Blood, 2010; 115: 1650). These results raised the possibility that the functional regulation of VWF by ADAMTS13 could also play a role in coronary ischemic events such as myocardial infarction. To address this issue, we have used a mouse model of experimental myocardial infarction. The left anterior descending coronary artery in mice was ligated at 2 mm downstream from the origin under thoracotomy with ventilator-assisted respiration, and the cardiac function was evaluated with M-mode echocardiography after 7 days of operation. We compared 20 wild-type (WT) mice and 20 Adamts13 −/− (KO) mice, all of which were 12–14 weeks of age, healthy and fertile. Significantly (p < 0.01) decreased ejection fraction (EF; 44.0±6.7%) and increased left ventricular end-diastolic diameter (LVDd; 4.68±0.69 mm) of KO mice, as compared to WT (EF; 62.7±13.0% and LVDd; 3.77±0.56 mm, respectively), revealed that cardiac functions were apparently more impaired in KO mice. In addition, these reduced cardiac functions observed in KO mice were improved to an extent comparable to those of WT mice by the bolus injection of recombinant human ADAMTS13 (rhADAM; 3 μg/mouse, n=20) just after the operation (KO mice + rhADAM, EF; 58.2.±9.9% and LVDd; 3.16±0.52 mm). Consistent with echocardiography data, histological studies demonstrated the significantly (p < 0.01) higher infarct ratio in myocardium of KO mice (WT; 37.3±18.4%, KO; 59.1±16.3%, KO + rhADAM; 33.7±24.4%). Our results indicate that ADAMTS13, as seen in the case of brain ischemic stroke, plays a protective role for myocardium in coronary artery ischemia, improving myocardial functions and the severity of heart failure. Proper functional regulation of VWF-dependent thrombotic or inflammatory responses by ADAMTS13 could reduce thrombotic occlusion of microvasculature including leukocyte plugging, contributing to better local microcirculation which is crucial for tissue or organ functions. Disclosures: No relevant conflicts of interest to declare.

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