Premium
Synergistic effect of palmitate and nicotine treatments in diabetic heart (LB560)
Author(s) -
Arunachalam Gnanapragasam,
Samuel Samson,
Ghosh Suparna,
Ding Hong,
Machaca Khaled,
Triggle Chris
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.lb560
Subject(s) - medicine , heart failure , endocrinology , diabetic cardiomyopathy , pdk4 , diabetes mellitus , nicotine , hypertriglyceridemia , chemistry , cardiomyopathy , biochemistry , gene expression , triglyceride , cholesterol , gene
Background: Metabolic disorders (hyperglycemia, dyslipidemia, hypertension) contribute to the development and progression of cardiovascular disease in individuals with type 2 diabetes. Risk factors such as obesity and cigarette smoking are also strongly associated with exacerbation of diabetes‐associated heart failure. Obesity is associated with hypertriglyceridemia and elevated circulating free fatty acids (FFA), result in endothelial dysfunction and heart failure. Recent findings have demonstrated that alterations in cardiac energy metabolism are primarily connected with the development of cardiomyopathy in the diabetic heart. Methods: In the current study, the synergistic effects of FFA flux and nicotine treatment were investigated in‐vitro, using endothelial (MMECs), myoblast (C2C12) and cardio myoblast (H9C2) cell culture models under hyperglycemic conditions. Results: Our data indicate that cells treated with palmitate/nicotine showed increased E2F1 transcription with altered PPAR‐α expression‐a transcription factor involved in lipid metabolism. In addition, combined effects of palmitate/nicotine on Rb‐phosphorylation and activation of cyclin‐dependent kinases (CDKs) and their cyclin partners (A/E/D), the upstream regulators of E2F1‐transcription were also studied. Conclusion: Our data demonstrate that elevated FFA and nicotine change PPAR‐α/CDK/E2F1 gene expression and promote apoptosis and genomic instability thus revealing a potential molecular mechanism in obesity and cigarette smoking‐associated heart failure in diabetic milieu. Grant Funding Source : This project was funded by grant NPRP 9‐413‐3‐104