Abstract | AIM: METHODS: DCM was induced in Wistar rats by low-dose streptozotocin-high-fat diet for 12 weeks. Cardiac expression of Cdc42, Pak1 and miR-30c, and hypertrophy markers ( ANP and β-MHC) was studied in DCM vs control rats and in high- glucose (HG)-treated H9c2 cardiomyocytes. RESULTS: Diabetic rats showed cardiomyocyte hypertrophy, increased heart-to- body weight ratio, and an increased expression of ANP and β-MHC. Cardiac expression of Cdc42 and Pak1 genes was increased in diabetic hearts and in HG-treated cardiomyocytes. miR-30c was identified to target Cdc42 and Pak1 genes, and cardiac miR-30c expression was found to be decreased in DCM rats, patients with DCM, and in HG-treated cardiomyocytes. miR-30c overexpression decreased Cdc42 and Pak1 genes and attenuated HG-induced cardiomyocyte hypertrophy, whereas miR-30c inhibition increased Cdc42 and Pak1 gene expression and myocyte hypertrophy in HG-treated cardiomyocytes. CONCLUSION: Downregulation of miR-30c mediates prohypertrophic effects of hyperglycemia in DCM by upregulation of Cdc42 and Pak1 genes.
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Authors | Satish K Raut, Akhilesh Kumar, Gurinder B Singh, Uma Nahar, Vibhuti Sharma, Anupam Mittal, Rajni Sharma, Madhu Khullar |
Journal | Cardiovascular therapeutics
(Cardiovasc Ther)
Vol. 33
Issue 3
Pg. 89-97
(Jun 2015)
ISSN: 1755-5922 [Electronic] England |
PMID | 25781190
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 John Wiley & Sons Ltd. |
Chemical References |
- MIRN30b microRNA, human
- MYH7 protein, human
- MicroRNAs
- Streptozocin
- Atrial Natriuretic Factor
- PAK1 protein, human
- p21-Activated Kinases
- Cardiac Myosins
- Myosin Heavy Chains
- cdc42 GTP-Binding Protein
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Topics |
- Animals
- Atrial Natriuretic Factor
(metabolism)
- Cardiac Myosins
(metabolism)
- Cardiomegaly
(pathology)
- Cell Line
- Diabetes Mellitus, Experimental
- Diabetic Cardiomyopathies
(pathology)
- MicroRNAs
(metabolism)
- Myocytes, Cardiac
(metabolism)
- Myosin Heavy Chains
(metabolism)
- Rats
- Rats, Wistar
- Streptozocin
- Up-Regulation
- cdc42 GTP-Binding Protein
(biosynthesis)
- p21-Activated Kinases
(biosynthesis)
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