Abstract 11227: Quantitative Transcriptome Analysis Using Next Generation Sequencer Reveals Significant Alternations of Vascular Endothelial Gene Expression in Heart Failure
Since a variety of gene alternations are involved in heart failure (HF), identifying key functional modules associated with HF is a challenging task. In HF, endothelial function is significantly attenuated and reduced skeletal muscle blood flow and correlates with the severity of symptoms. Improvement of its dysfunction is an important target in the treatment of HF. We investigated the global transcriptome analysis of femoral artery from tachycardia induced HF dogs using next generation genome sequencers. Next, we examined therapeutic effects of statin (0.3mg/kg/day, n=7) on vascular endothelial function and that gene expression. The mRNA sequence reads aligned with ~15000 of the 21407 genes using the human genome19 database. The analysis identified significantly up-regulated interleukin-related genes and p53 pathways which are stimulated by small G proteins such as Ras and Rho and regulate cell cycles, inflammation and proliferation. Pitavastatin significantly improved femoral blood flow responses by acetylcholine(HF 92.4±6.4 ml/min vs Ptavastatin 144.3±9.8 P<0.05), suppressed superoxide production (HF 17.3±2.1RLU/mg/min vs Ptavastatin10.2 ±1. 1RLU/mg/min P<0.05) and NADPH oxidase activity (HF 620.9±70.4RLU/mg/min vs Ptavastatin 388.7±40.5 RLU/mg/min P<0.05) in HF. The agent decreased the levels of p53, p21 and interleukin-1 mRNAs expressions. We can conclude that the global transcriptome analysis can provide new insights into vascular cellular mechanisms and therapeutic effects of statins in HF.
- © 2013 by American Heart Association, Inc.