Atherosclerosis is the major cause of ischemic heart disease and stroke, the leading causes of mortality worldwide. To develop better therapies, Dr. Yue’s group focuses on investigating the underlying mechanism of atherosclerosis, the root cause of cardiovascular diseases and brain stroke. The prominent feature of atherosclerosis is the formation of foam cells, the lipid-laden macrophages. Foam cells accelerate the progression of atherosclerosis by enhancing the inflammatory responses inside the arterial walls. Lipid uptake of macrophages is mainly mediated by CD36. TRPM2 is a heat-sensitive and calcium-permeable ion channel that is usually activated by oxidative stress conditions, and oxidative stress is also the prominent feature of atherosclerosis.
Recently, Pengyu Zong, a graduate student in Yue lab, discovered that TRPM2 plays a critical role in the development and progression of atherosclerosis by promoting CD36 activation in macrophages (as shown in the illustrating image). Trpm2 deletion inhibits macrophage infiltration, foam cell formation and subsequent pro-inflammatory activation. Both global and macrophage-specific Trpm2 deletion attenuates HFD-induced atherosclerosis. Taken together, their studies reveal an important mechanism for understanding atherogenesis, and suggest TRPM2 as a promising target for screening more effective therapies for atherosclerosis. Moreover, CD36 is highly expressed in many other cell types, especially endothelial cells, suggesting that TRPM2-CD36 coupling may also contribute to the pathogenesis of endothelial-dysfunction-related diseases, such as Alzheimer disease and stroke.
Pengyu’s work has recently been published in Nature Cardiovascular research(https://www.nature.com/articles/s44161-022-00027-7; https://www.nature.com/articles/s44161-022-00037-5). To read the press release published in UConn Today, please click here (https://today.uconn.edu/2022/03/deleting-a-protein-in-mice-prevents-cardiovascular-disease/). Pengyu also won a travel award for attending Vascular Discovery meeting held from 05/10-05/14 at Seattle, WA (featured here).