Graphical Abstract.

Schematic representation of the main findings regarding (i) the genome-wide association study (GWAS) analysis of the Gutenberg Health Study (GHS), and (ii) the translational approach in the transgenic vascular smooth muscle cell-specific tubulin-folding cofactor E (TBCE) knockout murine model. Arrows represent activation/induction pathways, T lines present inhibition pathways, while dotted arrows present cellular crosstalk between endothelial and smooth muscle cells as observed in vivo. Cnx, calnexin; ER, endoplasmic reticulum; IRE1α, inositol-requiring enzyme 1α; PDI, protein disulfide-isomerase; PERK, protein kinase RNA-like endoplasmic reticulum kinase; SNP, single-nucleotide polymorphism; TBCE, tubulin-folding cofactor E; TUDCA, tauroursodeoxycholic acid.