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Suppression of cardio‐protective molecules by diabetic marker miR‐29: a mechanism for the high rate of cardiac damage in diabetes? (1086.6)
Author(s) -
Arnold Nicholas,
Koppula Purushotham,
Pulakat Lakshmi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1086.6
Subject(s) - diabetic cardiomyopathy , medicine , endocrinology , diabetes mellitus , heart failure , masson's trichrome stain , apoptosis , downregulation and upregulation , myocyte , cardiac function curve , biology , immunohistochemistry , cardiomyopathy , biochemistry , gene
Diabetic marker miRNA‐29 (miR‐29) is up‐regulated by pro‐inflammatory cytokines and hyperglycemia. miR‐29 induced suppression of MCL‐1, a protein essential for mitochondrial function and cell survival, occurs in pancreatic β‐cell death. We hypothesized that conditions that increase miR‐29 levels in heart would promote suppression of MCL‐1 and increase cardiomyocyte cell death. Since Rapamycin (Rap) is known to promote diabetes, we further posited that Rap treatment (750 µg/kg/day; 6 weeks) would increase miR‐29 and suppress MCL‐1 in heart tissues of Zucker Diabetic Fatty (ZDF) rat, a rodent model for the progression of Type 2 Diabetes. Rap treatment attenuated plasma insulin (INS) levels implying development of insulinopenia; however, hyperglycemia persisted. q‐PCR showed a significant increase in miR‐29a, b, and c and suppression of MCL‐1 (p<0.01) in ZDF heart. Rap treatment also resulted in significant loss of cardiomyocytes as visualized by histopathological analysis by H & E and Masson's trichrome staining. Moreover, Rap treatment increased miR‐29 levels and suppressed MCL‐1 mRNA and protein levels in mouse atrial cardiomyocytes (10nM; 12hr) and in human coronary artery smooth muscle cells (20nM; 12hr). These data suggest that MCL‐1 regulation via miR‐29 family in INS‐responsive tissues is conserved across species and contributes to cardiomyocyte loss that can promote heart failure in diabetes. Grant Funding Source : NIH: 1R01HL118376‐01