Studying the Effect of High Glucose-Treated Macrophages on Vascular Smooth Muscle Cell Phenotypic Switch and Calcification

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Patients with diabetes or hypertension were linked with higher rate of mortality in CKD patients. Among all the CKD-related complications, much attention has been paid to the vascular calcification. Arterial medial calcification is recognized detrimental to cardiovascular outcome. The arterial stiffness in CKD patients is characterized by arterial intima-media hypertrophy resulting from alterations of the intrinsic properties of arterial wall properties. Phenotype changes of vascular smooth muscle cells (SMCs), cross-talks between endothelial cells or monocytes/macrophages through mechanical mechanisms are possible involving pathogenesis. People with CKD are at high risk for atherosclerosis. The early stage of atherogenesis involves adhesion and transmigration of monocytes to vascular wall, which are located in close proximity to SMCs. SMCs located in normal arterial media exhibit a contractile phenotype, whereas SMCs in atherosclerotic plaques show a synthetic phenotype. In addition, these SMCs also respond to mechanical forces, such as cyclic stretch, during the progression of vascular diseases and when proliferation increases, inflammation and cell dysfunction advance. A correlation has been established between CKD and cardiovascular diseases. However, the interplay of macrophages, SMCs, and cyclic stretch during the regulation of vascular calcification remains poorly understood. The aims of this study are to investigate the effects of high glucose (HG)-treated macrophages on phenotypic switch and calcification of vascular SMCs. In addition, the toll-like receptor (TLR)-mediated intracellular signal transduction in SMCs will be investigated. The regulatory mechanisms of mechanical forces (e.g. cyclic stretch) on SMCs gene expression and function will also be examined. The results from this study may provide insights into the mechanisms contributing to vascular cell activation in patients with CKD.

Project ID:PC10408-2448
External Project ID:MOST104-2314-B182-037