Year: 2020
Type: article
Abstract: Autophagy is an essential cellular quality control process that has emerged as a critical one for vascular homeostasis. Here, we show that trichoplein (TCHP) links autophagy with endothelial cell (EC) function. TCHP localizes to centriolar satellites, where it binds and stabilizes PCM1. Loss of TCHP leads to delocalization and proteasome-dependent degradation of PCM1, further resulting in degradation of PCM1's binding partner GABARAP. Autophagic flux under basal conditions is impaired in THCP-depleted ECs, and SQSTM1/p62 (p62) accumulates. We further show that TCHP promotes autophagosome maturation and efficient clearance of p62 within lysosomes, without affecting their degradative capacity. Reduced TCHP and high p62 levels are detected in primary ECs from patients with coronary artery disease. This phenotype correlates with impaired EC function and can be ameliorated by NF-κB inhibition. Moreover, Tchp knock-out mice accumulate of p62 in the heart and cardiac vessels correlating with reduced cardiac vascularization. Taken together, our data reveal that TCHP regulates endothelial cell function via an autophagy-mediated mechanism.
Source: EMBO Reports
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Awards: Trichoplein: role for a novel regulator in the endothelial cell function in diabetes, G2299036540, G272177980, Identification and characterisation of a vessel wall endothelial progenitor cell, and its potential, G3124682028, G388216973, Epigenetics and lncRNA control of angiogenesis, G5785785754, G6086101503, Inter-cellular trafficking and regulation of microRNA-503 expression in diabetes-induced microvascular complications, G6199128650, IMPC: Investigating the role of Trichoplein (TCHP) in post-ischaemic vascular repair, Derivation and characterisation of endothelial cells from induced pluripotent stem cells in patients with atherosclerosis, The BHF Butler Senior Clinical Research Fellowship: High-sensitivity cardiac troponin and coronary heart disease
OpenAlex ID: W3017484804