Abstract 574: Regulation of Vascular Smooth Muscle Cells Phenotype by the Adhesion of Platelets to Endothelial Cells
Objective: Platelets can regulate endothelial cell genes expression through their adhesion to the subendothelium in response to vascular injury. Recently it has been reported that some endothelial cells (ECs)-secreted genes can modulate vascular smooth muscle cells (VSMCs) phenotypic transformation by ECs/VSMCs co-culture. However, little is known about the effects of platelets adhesion to ECs interaction on VSMCs phenotype. In this study, we investigated the role of some genes secreted by platelets adhesion to EC in regulating SMC phenotypic transformation.
Methods and Results: By Q-RT-PCR, expression of PAI-1, MMP-2 and MMP-9 were up-regulated in ECs after platelets adhesion to ECs comparing to ECs monoculture alone. In migration (scratch) and proliferation (CCK-8) assays, platelets adhesion to ECs increased EC migration-promoting activity and proliferative activity. After adhesion of platelets to ECs/VSMCs co-culture, expression of VSMCs contractile apparatus SM-MHC, Smoothelin-B, SMA and SM22a were significantly decreased comparing to ECs/VSMCs co-culture by Q-RT-PCR, but decreasing slightly in adhesion with platelets from type 2 diabetes. Conversely, it increased the expression of synthetic marker Smemb, CCND-1, CCND-2. Further analysis found that platelets adhesion to ECs/VSMCs co-culture significantly increased VSMCs migration-promoting activity and proliferative activity. In Gelatin Zymography assays, there were high levels of MMP-2 and MMP-9 after adhesion of platelets to ECs/VSMCs co-culture comparing to ECs/VSMCs co-culture alone.
Conclusion: These results offer important insights into the mechanisms controlling phenotypic modulation of VSMCs by platelets adhesion to ECs, and help to explain the effects of platelets-ECs-VSMCs interaction on VSMCs contractile/synthetic, migration, and proliferation, suggesting that the adhesion of platelets to ECs is a key process in regulating phenotypic switch of VSMCs.
Author Disclosures: M. Luo: None. M. Zeng: None. M. Ren: None. R. Li: None. X. Deng: None. N. Chen: None. Y. Yang: None. J. Wu: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.