Mitochondrial Dysfunction in Diabetic Cardiomyopathy

Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4

Mohamed Abd Elaziz Wassef, Ola M. Tork, Laila A. Rashed, Walaa Ibrahim, Heba Morsi, Dina Mohamed Mekawy Rabie

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4. All treatments were started after 6 weeks from induction of diabetes and continued for the next 4 weeks. Blood samples were collected for assessment of glucose, insulin, and cardiac enzymes. Hearts were removed and used for isolated heart studies, and gene expression of: myocyte enhancer factor-2 (Mef2), peroxisome proliferator-activated receptor gamma coactivator1-alpha (PGC1α), nuclear factor kappa B (NFKB) and autophagic markers: light chain 3 (LC3) and beclin by real-time reverse transcription-polymerase chain reaction. The cardiac mitochondrial protein levels of cardiolipin and uncoupler protein 2 (UCP2) were assessed by ELISA and western blot technique, respectively. Treated groups showed significant improvement in left ventricular function associated with improvement in the cardiac injury and myopathic markers compared to the non treated diabetic group. NFKB was down-regulated while cardiolipin, PGC1α, LC.3 and beclin were up-regulated in all treated groups. These data suggest that the cardioprotective effects of MSCs, exendin-4 or pioglitazone based on their ability to improve mitochondrial functions through targeting inflammatory and autophagy signaling. The co- administration of pioglitazone or exendin-4 with MSCs showed significant superior improvement compared with MSCs alone, indicating the ability to use them in supporting cardioprotective effects of MSCs.

Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalExperimental and Clinical Endocrinology and Diabetes
Volume126
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Diabetic Cardiomyopathies
Peroxisome Proliferator-Activated Receptors
pioglitazone
Mesenchymal Stromal Cells
Cardiolipins
NF-kappa B
PPAR gamma
MEF2 Transcription Factors
Glucagon-Like Peptide 1
exenatide
Mitochondrial Proteins
Autophagy
Wounds and Injuries
Diabetes Complications
Left Ventricular Function
Reverse Transcription
Mitochondria
Bone Marrow
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

  • autophagy
  • cardiolipin
  • myocyte enhancer factor-2
  • NF- κ B
  • PGC1α
  • uncoupler protein 2

Cite this

Wassef, Mohamed Abd Elaziz ; Tork, Ola M. ; Rashed, Laila A. ; Ibrahim, Walaa ; Morsi, Heba ; Rabie, Dina Mohamed Mekawy. / Mitochondrial Dysfunction in Diabetic Cardiomyopathy : Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4. In: Experimental and Clinical Endocrinology and Diabetes. 2018 ; Vol. 126, No. 1. pp. 27-38.
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Mitochondrial Dysfunction in Diabetic Cardiomyopathy : Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4. / Wassef, Mohamed Abd Elaziz; Tork, Ola M.; Rashed, Laila A.; Ibrahim, Walaa; Morsi, Heba; Rabie, Dina Mohamed Mekawy.

In: Experimental and Clinical Endocrinology and Diabetes, Vol. 126, No. 1, 01.01.2018, p. 27-38.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Rashed, Laila A.

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AU - Morsi, Heba

AU - Rabie, Dina Mohamed Mekawy

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