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.
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