taurochenodeoxycholic-acid and Progeria

taurochenodeoxycholic-acid has been researched along with Progeria* in 1 studies

Other Studies

1 other study(ies) available for taurochenodeoxycholic-acid and Progeria

ArticleYear
Progerin accelerates atherosclerosis by inducing endoplasmic reticulum stress in vascular smooth muscle cells.
    EMBO molecular medicine, 2019, Volume: 11, Issue:4

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by progerin, a mutant lamin A variant. HGPS patients display accelerated aging and die prematurely, typically from atherosclerosis complications. Recently, we demonstrated that progerin-driven vascular smooth muscle cell (VSMC) loss accelerates atherosclerosis leading to premature death in apolipoprotein E-deficient mice. However, the molecular mechanism underlying this process remains unknown. Using a transcriptomic approach, we identify here endoplasmic reticulum stress (ER) and the unfolded protein responses as drivers of VSMC death in two mouse models of HGPS exhibiting ubiquitous and VSMC-specific progerin expression. This stress pathway was also activated in HGPS patient-derived cells. Targeting ER stress response with a chemical chaperone delayed medial VSMC loss and inhibited atherosclerosis in both progeria models, and extended lifespan in the VSMC-specific model. Our results identify a mechanism underlying cardiovascular disease in HGPS that could be targeted in patients. Moreover, these findings may help to understand other vascular diseases associated with VSMC death, and provide insight into aging-dependent vascular damage related to accumulation of unprocessed toxic forms of lamin A.

    Topics: Animals; Aorta; Apoptosis; Atherosclerosis; Disease Models, Animal; Endoplasmic Reticulum Stress; Gene Expression; HSP90 Heat-Shock Proteins; Kaplan-Meier Estimate; Lamin Type A; Longevity; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Smooth, Vascular; Progeria; Protein Disulfide-Isomerases; Taurochenodeoxycholic Acid; Unfolded Protein Response

2019