The functional role of cellular senescence during vascular calcification in chronic kidney disease

Abstract

Overview of the role of cellular senescence in regulating vascular calcification. The complex landscape of CKD hastens the senescence of vascular endothelial cells (VECs) and undermines their functional integrity, exhibiting a distinctive profile characterized by the reduced expression of nitric oxide (NO) and an elevation in reactive oxygen species (ROS). Senescent VECs release microvesicles (MVs) to trigger senescence and calcification in VSMCs. On the other hand, senescent VECs attract monocytes to the endothelium and induce the proliferation and migration of VSMCs. Pro-inflammatory phenotypic macrophages subsequently promote VSMC calcification by stimulating carbonic anhydrase I (CA1) and CA2 via secreting TNFα, or NLRP3 inflammasome. Mesenchymal stromal cells (MSCs) and adventitial fibroblasts (AFs) exhibit a potential for differentiation, with the ability to transform into VECs and VSMCs, contributing to the replenishment of senescent cells. However, the proliferation and differentiation capacities of senescent MSCs and AFs are diminished. (Figure presented.)