Dr Ashish Misra
Unit Leader, Heart Research Institute (HRI)
Smooth muscle cells (SMCs) play a key role in vascular diseases. However, mechanisms regulating clonal expansion and fate of pre-existing SMCs in vascular disorders remain poorly defined. Here we show that multiple SMC progenitors mix to form the aorta during embryonic development. In contrast, during atherogenesis, a single SMC gives rise to smooth muscle-derived cells and clonally expands, hyperproliferates and initially coat the cap of atherosclerotic plaques. Subsequently, lineage-tracking techniques show that in atherogenesis, clonally derived cells further proliferative and invade the plaque core, comprising the majority of plaque cells. Furthermore, global integrin Itgb3 deletion or transplantation of Itgb3(-/-) bone marrow results in recruitment of multiple pre-existing SMCs into plaques. Our results suggest SMC contribution to atherogenesis is regulated by integrin β3-mediated pathways in both SMCs and bone marrow-derived cells. In sum, we have identified a pool of SMC progenitors that are critical for the pathogenesis of vascular disorders, and therapeutic strategies targeting these cell types promise to have profound implications.
Dr Ashish Misra received his Master’s degree from the Indian Institute of Technology, Kanpur, India, and his PhD in cell and molecular biology from Nanyang Technological University, Singapore in 2011. Dr Misra joined HRI from Yale Cardiovascular Research Center (YCVRC), Yale University where he was a Postdoctoral Associate. He is a recipient of the prestigious Yale Brown-Cox Postdoctoral Fellowship. His research focuses on blood vessel wall development and the pathogenesis of diverse cardiovascular diseases. His recent work demonstrated the molecular processes and signals that are required for blood vessel wall patterning and how aberrant molecular signalling leads to vascular abnormalities.