Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells.

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin-induced atherosclerosis is prevented inandmice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively.mice were undistinguishable frommice with ubiquitous progerin expression, in contrast with the ameliorated progeroid phenotype ofmice. To study atherosclerosis, we generated atheroprone mouse models by overexpressing a PCSK9 gain-of-function mutant. Whileandmice developed a similar level of excessive atherosclerosis, plaque development inmice was reduced to wild-type levels. Our studies demonstrate that progerin suppression in VSMCs, but not in ECs, prevents exacerbated atherosclerosis in progeroid mice.