Paradoxical effect of fat diet in matrix metalloproteinases induced mitochondrial dysfunction in diabetic cardiomyopathy

被引：6

作者：

Gliozzi, Micaela ^{[1
,2
]}

Scarano, Federica ^{[1
,2
]}

Musolino, Vincenzo ^{[1
,2
]}

Carresi, Cristina ^{[1
,2
]}

Scarcella, Antonino ^{[1
,2
]}

Nucera, Saverio ^{[1
,2
]}

Scicchitano, Miriam ^{[1
,2
]}

Ruga, Stefano ^{[1
,2
]}

Bosco, Francesca ^{[1
,2
]}

Maiuolo, Jessica ^{[1
,2
]}

Macri, Roberta ^{[1
,2
]}

Zito, Maria Caterina ^{[1
,2
]}

Oppedisano, Francesca ^{[1
,2
]}

Guarnieri, Lorenza ^{[1
,2
]}

Mollace, Rocco ^{[1
,2
]}

Palma, Ernesto ^{[1
,2
]}

Muscoli, Carolina ^{[1
,2
]}

Mollace, Vincenzo ^{[1
,2
]}

机构：

[1] Magna Graecia Univ Catanzaro, Inst Res Food Safety Hlth IRC FSH, Viale Europa, I-88100 Catanzaro, Italy

[2] Nutramed Scarl, Roccelletta Borgia, Catanzaro, Italy

来源：

JOURNAL OF CARDIOVASCULAR MEDICINE | 2021年 / 22卷 / 04期

关键词：

diabetic cardiomyopathy; hyperlipidaemia; matrix metalloproteinases; mitochondrial dysfunction; oxidative stress;

D O I：

10.2459/JCM.0000000000001046

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims Diabetic cardiomyopathy represents the main cause of death among diabetic people. Despite this evidence, the molecular mechanisms triggered by impaired glucose and lipid metabolism inducing heart damage remain unclear. The aim of our study was to investigate the effect of altered metabolism on the early stages of cardiac injury in experimental diabetes. Methods For this purpose, rats were fed a normocaloric diet (NPD) or a high fat diet (HFD) for up to 12 weeks. After the fourth week, streptozocin (35 mg/kg) was administered in a subgroup of both NPD and HFD rats to induce diabetes. Cardiac function was analysed by echocardiography. Matrix metalloproteinases (MMPs) activity and intracellular localization were assessed through zymography and immunofluorescence, whereas apoptotic and oxidative markers by immunohistochemistry and western blot. Results Hyperglycaemia or hyperlipidaemia reduced ejection fraction and fractional shortening as compared with control. Unexpectedly, cardiac dysfunction was less marked in diabetic rats fed a hyperlipidaemic diet, suggesting an adaptive response of the myocardium to hyperglycaemia-induced injury. This response was characterized by the inhibition of N-terminal truncated-MMP-2 translocation from endoplasmic reticulum into mitochondria and by superoxide anion overproduction observed in cardiomyocytes under hyperglycaemia. Conclusion Overall, these findings suggest novel therapeutic targets aimed to counteract mitochondrial dysfunction in the onset of diabetic cardiomyopathy.

引用

页码：268 / 278

页数：11

共 53 条

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