Abstract P148: Urotensin II Impairs Cardiac Functions and Proliferation of Cardiac Side Population Cells in Mice During Chronic Pressure Overload.

Abstract

Urotensin II (UII), a potent vasoactive “somatostatin-like” peptide, has been known to play a role in cardiovascular diseases including cardiac hypertrophy and heart failure. But its effect on cardiac side population cells (CSPs), one of somatic stem cells in the heart potentially participating in cardiac protection after injury, is unclear. The present study was therefore conducted to examine influences of UII on the differentiation, proliferation and function of CSPs. CSPs were isolated from neonatal rat hearts by fluorescence-activated cell sorting (FACS) and cultured in the absence or at the presence of UII. The expressions of alpha-cardiac myosin heavy chain, alpha-smooth muscle actin and Von Willebrand factor at mRNAs and protein levels were analyzed by reverse transcriptional PCR (RT-PCR) and immunofluoresence to evaluate the differentiation of CSPs into cardiomyocytes, smooth muscle cells and endothelial cells, respectively. The proliferation of CSPs was assessed by Luminescent Cell Viability Assay. The influence of UII on the proliferation of CSPs in vivo was also evaluated by FACS. Our results revealed that UII did inhibit the proliferation of CSPs through up-regulation of phosphorylated c-Jun N-terminal protein kinase (JNK), although it didn’t affect the differentiation of cultured CSPs into cardiaomyocytes, smooth muscle cells and endothelial cells. In vivo experiments also showed that injection of UII reduced the number of CSPs and impaired cardiac functions compared with vehicle injection in mice subjected to a chronic pressure overload, and an UII antagonist urantide induced a preserved cardiac function with an increased number of CSPs. These data indicate that UII reduces the number of CSPs by inhibiting the proliferation of CSPs possibly through increase of JNK phosphorylation, and blockage of UII may be a useful strategy for cardiac protection in the hypertensive.