Impact of Senescent Endothelial Cells on Vascular Smooth Muscle Cells

Abstract

Cellular senescence was at one time thought to be benign, but it is becoming evident that senescent cells are pro-inflammatory and may be associated with other deleterious consequences in aging organisms that accumulate senescent cells over time. In particular, senescent endothelial cells are known to secrete markedly more pro-inflammatory factors than non-senescent cells, and more disturbingly, may also incite pro-inflammatory secretion in the healthy non-senescent cells along with other negative functional changes. To investigate this issue, we co-cultured human microvascular smooth muscle cells (VSMC) with senescent (SEN) or early-passage (EP) human endothelial cells (EC), separated by a permeable membrane to allow both VSMC and EC to communicate with secreted factors. We found that the coculture of VSMC with EC markedly and synergistically elevated secreted pro-inflammatory factors, IL-6, IL-8, and MCP-1. While both SEN and EP cells promoted the cytokine and chemokine release by comparable levels, the amount released in SEN EC – VSMC coculture was 1.5- to 2- fold greater than in EP EC – VSMC co-culture. In addition, the beta 1 subunit of soluble guanylate cyclase, an NO receptor that promotes vasodilation, was decreased in the VSMC from SEN EC – VSMC coculture, but not in EP EC – VSMC coculture. These findings suggest the potential role of senescent EC in aggravating hypertension and persistent inflammatory disorder that are common in older individuals.