Abstract 140: BMI- and Gender-specific Increase of MAP2K3/p38 Activity in Human Cardiac Hypertrophy

• Published in: Circulation research 2016-07, Vol.119 (suppl_1)
• Main Authors: Newman, Mackenzie, Infanto, Aniello M, Watson, Michael J, Hull, Robert W, Yu, Han-Gang
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.119.suppl_1.140

Abstract only Introduction: MAP2K3 is a stress-induced kinase and its role cardiac hypertrophy has been controversial: while in vitro studies have displayed a positive correlation in activity with hypertrophy, in vivo studies have shown a negative association. Its direct downstream target, p38α MAPK, has been shown to be in activated in hypertrophic and failed hearts, but this has not been explored with regard to gender or BMI. Hypothesis: Early activation of p38 MAPK in hypertrophy is influenced by gender and BMI. Methods: Human heart samples were grouped into non-failed (NF), left ventricular hypertrophy (LVH), and NF without LVH (control). BMI < 25 was considered “lean”, 25 < BMI < 30 was considered overweight, and BMI > 30 was considered “obese”. RNA-Seq was used to generate cardiac gene expression profiles. Immunoblots were used to examine protein expression of MAP2K3, p38, and activated p38 (pp38; phospho-T180 and Y182). Results: We found that MAP2K3 mRNA levels were increased in obese males by 134% with LVH compared to non-LVH controls (FPKM: LVH = 19.2±3.5, n=3; non-LVH = 8.2±1.9, n=3; FPKM = Fragments Per Kilobase of transcript per Million mapped reads), without statistical significance (p>0.05). MAP2K3 protein expression was 5-fold higher in LVH (1.24±0.20, n=9) versus non-LVH hearts (0.25±0.03, n=15) (p25 = 0.63 ± 0.03 (n=7), M_BMI