Biomechanical regulation of leptin expression in vascular smooth muscle both in vivo and in vitro: a novel vascular‐proteomic and physiological approach (866.9)

Abstract

Hypertension is considered one of the major risk factors in developing cardiovascular diseases. Hemodynamic abnormality in hypertension is associated with structural and functional alterations which are mainly mediated via leptin. Molecular mechanisms associated with leptin‐mediated blood vessels remodeling both in vivo and in vitro have not been fully elucidated. In this study, we investigated the effect of partial portal vein ligation (PPVL) on leptin expression in vascular smooth muscle (VSMC) and secretion. We used blood vessels organ culture under mechanical stretch in order to investigate molecular mechanisms of leptin‐induced VSMC remodeling. Data showed that leptin expression and ROS production significantly increased in VSMC after 7 and 14 days post PPVL. A significant increase in serum leptin levels was observed in PPVL. Exposing the blood vessels to mechanical stretch (mimicking hypertension) significantly increased nuclear translocation of GATA‐4 and NFAT which were attenuated by the co‐administration of an anti‐leptin receptor antibody and the RhoA inhibitor C3. In addition, vascular‐proteomics platform was performed assessing differential proteome/systems biology profile between stretched and unstretched blood vessels to investigate the underlying mechanisms involved in vascular hypertrophy. A differential display of proteins were identified (7 proteins were upregulated vs. 12 downregulated) using PANTHER (Protein Analysis Through Evolutionary Relationships) system and Pathway Studio 8. Our results indicate that the activation of GATA‐4 & ROS production plays a pivotal role in hypertension signaling, leading to leptin synthesis and VSMC hypertrophy. Grant Funding Source: Supported by CNRS and MPP at AUB