Lobov, A., et al. “Proteomic profiling of endothelial cells treated with calciprotein particles.” Atherosclerosis 355 (2022): 2-3. https://doi.org/10.1016/j.atherosclerosis.2022.06.236

Abstract

Background and Aims: Calciprotein particles (CPPs), generated in human blood to cope with mineral stress, represent both a physiological tool for aggregating excessive calcium and phosphate and a trigger of pathological events upon the internalisation by endothelial cells (ECs). However, unbiased proteomic profiling of CPP-treated ECs have not been performed.

Methods: Primary human coronary artery (HCAEC) and internal thoracic artery ECs (HITAEC) were exposed to primary (CPP-P) or secondary (CPP-S) CPPs for 24 hours. Label-free proteomic profiling was performed by liquid chromatography-tandem mass spectrometry with ion mobility (TimsToF Pro). Bioinformatic analysis was conducted using PEAKS Studio Xpro and R software environment. Proteins identified with false discovery rate <1% and having ≥2 unique peptides were included into further analysis.

Results: We found significant differences in global expression profile of HCAEC exposed to either CPP-P (420/466 up/downregulated proteins) or CPP-S (389/447 up/downregulated proteins). HITAEC showed less pronounced response to both CPP-P (209/221 up/downregulated proteins) and CPP-S (234/207 up/downregulated proteins). Analysis of GO terms identified certain categories upregulated upon the exposure to CPP-P or CPP-S (cellular respiration, regulation of cytochrome c release from mitochondria, response to oxidative stress, cellular response to reactive oxygen species, response to hydrogen peroxide, response to organonitrogen compound, response to endoplasmic reticulum stress, regulation of macroautophagy, vacuolar acidification, response to wounding).

Conclusions: CPP-P and CPP-S promote considerable changes in the proteomic (in particular mitochondrial- and lysosomal-related) profile of ECs.sa