Protective role of chaperone-mediated autophagy against atherosclerosis.
Julio Madrigal-MatuteJenny de BruijnKim van KuijkDario F Riascos-BernalAntonio DiazInmaculada TassetAdrián Martín-SeguraMarion J J GijbelsBianca SanderSusmita KaushikErik A L BiessenSimoni TianoMathieu BourdenxGregory J KrauseIan McCrackenAndrew H BakerHan JinNicholas E S SibingaJose Javier Bravo-CorderoFernando MacianRajat SinghPatrick C N RensenJimmy F P BerbéeGerard PasterkampJudith C SluimerAna Maria CuervoPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Chaperone-mediated autophagy (CMA) contributes to regulation of energy homeostasis by timely degradation of enzymes involved in glucose and lipid metabolism. Here, we report reduced CMA activity in vascular smooth muscle cells and macrophages in murine and human arteries in response to atherosclerotic challenges. We show that in vivo genetic blockage of CMA worsens atherosclerotic pathology through both systemic and cell-autonomous changes in vascular smooth muscle cells and macrophages, the two main cell types involved in atherogenesis. CMA deficiency promotes dedifferentiation of vascular smooth muscle cells and a proinflammatory state in macrophages. Conversely, a genetic mouse model with up-regulated CMA shows lower vulnerability to proatherosclerotic challenges. We propose that CMA could be an attractive therapeutic target against cardiovascular diseases.
Keyphrases
- vascular smooth muscle cells
- angiotensin ii
- cardiovascular disease
- mouse model
- single cell
- cell therapy
- endoplasmic reticulum stress
- endothelial cells
- signaling pathway
- oxidative stress
- genome wide
- heat shock protein
- climate change
- gene expression
- type diabetes
- endoplasmic reticulum
- coronary artery disease
- blood pressure
- cardiovascular events