Effects of administration of mesenchymal stem cells with and without PPAR-Þ agonist and Exendin-4 on mitochondrial dysfunction in diabetic cardiovascular complications in rats / Dina Mohamed Mekawy Rabie ; Supervised Mohamed Abdelaziz Wassef , Ola Mostafa Tork , Walaa Ibrahim Ali

Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Medical Biochemistry

Background: Diabetic cardiomyopathy (DCM) is defined as the cardiovascular damage present in diabetic patients, which is characterized by myocardial dilatation and hypertrophy, as well as a decrease in the systolic and diastolic function of the left ventricle. Therapy targeting mitochondria may provide novel ways to treat diabetes or to minimize the complications of diabetes or both. The PPAR agonists, in addition to their insulin-sensitizing properties,they have potential to affect cardiovascular disease risk in patients with type 2 diabetes .Bone marrow derived mesenchymal stem cells (MSCs) have shown great potential in cell therapy of solid organs. Exendin-4 is an analog of glucagon-like peptide-1(GLP-1). It promotes insulin gene transcription, synthesis and secretion. It inhibits the apoptosis of pancreatic Ý-cells at the gene level and promotes proliferation and regeneration. So we designed this work to evaluate the effect of MSCs, PPAR Þ agonist and Exendin-4 on diabetic cardiomyopathy. Methods: This work included: one hundred and five rats which were divided equally into seven groups: healthy control group, diabetic group that was induced by streptozotocin, diabetic group received MSCs only, diabetic group received Pioglitazone(PPAR Þ agonist) only, diabetic group received both MSCs and Pioglitazone, diabetic group received Exendin-4 only, diabetic group received both MSCs and Exendin-4 . Histopathological examination, gene expression of light chain 3(LC3), beclin, PGC alpha, nuclear factor kappa-light- chain-enhancer of activated B cells (NFmB) and Myocyte enhancer factor- 2 (Mef2) genes by real time reverse transcription-polymerase chain reaction (RT-PCR) in rat heart tissue, uncoupler protein 2 (UCP2) by western blot technique, serum levels of Mitochondrial cardiolipin and insulin by ELISA were assessed

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