LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

CTRP5 promotes transcytosis and oxidative modification of low-density lipoprotein and the development of atherosclerosis.

Photo by wulcan from unsplash

BACKGROUND AND AIMS Increased transcytosis of low-density lipoprotein (LDL) across the endothelium and oxidation of LDL deposited within the subendothelial space are crucial early events in atherogenesis. C1q/TNF-related protein (CTRP)… Click to show full abstract

BACKGROUND AND AIMS Increased transcytosis of low-density lipoprotein (LDL) across the endothelium and oxidation of LDL deposited within the subendothelial space are crucial early events in atherogenesis. C1q/TNF-related protein (CTRP) 5 is a novel secreted glycoprotein and its biological functions are largely undefined. METHODS Expression of CTRP5 was analyzed in sera and atherosclerotic plaques of patients with coronary artery disease (CAD). The role of CTRP5 in atherogenesis was investigated in vitro and in vivo. RESULTS We found CTRP5 serum levels were higher in patients with than without CAD (247.26 ± 61.71 vs. 167.81 ± 68.08 ng/mL, p < 0.001), and were positively correlated with the number of diseased vessels (Spearman's r = 0.611, p < 0.001). Increased expression of CTRP5 was detected in human coronary endarterectomy specimens as compared to non-atherosclerotic arteries. Immunofluorescence further showed that CTRP5 was predominantly localized in the endothelium, infiltrated macrophages and smooth muscle cells in the neointima. In vivo and in vitro experiments demonstrated that CTRP5 promoted transcytosis of LDL across endothelial monolayers, as well as the oxidative modification of LDL in endothelial cells. Mechanistically, we found that CTRP5 up-regulated 12/15-lipoxygenase (LOX), a key enzyme in mediating LDL trafficking and oxidation, through STAT6 signaling. Genetic or pharmacological inhibition of 12/15-LOX dramatically attenuated the deposition of oxidized LDL in the subendothelial space and the development of atherosclerosis. CONCLUSIONS These data indicate that CTRP5 is a novel pro-atherogenic cytokine and promotes transcytosis and oxidation of LDL in endothelial cells via up-regulation of 12/15-LOX.

Keywords: development atherosclerosis; ctrp5; density lipoprotein; low density; atherosclerosis; oxidative modification

Journal Title: Atherosclerosis
Year Published: 2018

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.