CTRP12 in cardiovascular and metabolic diseases: current status and future perspective

Figure 1. Schematic structure, cleavage and signaling specificity of CTRP12. CTRP12 is made up of four domains: a signal peptide for secretion, an N-terminal domain with multiple conserved Cys residues, a collagen domain with Gly-X-Y repeats, and a C-terminal globular domain homologous to the immune complement C1q. The full-length CTRP12 protein can be cleaved by furin to generate a globular isoform as the predominant form in circulation. Full-length CTRP12 preferentially activates Akt signaling to facilitate insulin-stimulated glucose uptake. Globular CTRP12 preferentially activates MAPK signaling.

Figure 2. Biological actions of CTRP12. CTRP12 is produced predominantly by adipocytes. As a multifunctional adipokine, CTRP12 participates in the regulation of lipid and glucose metabolism, inflammation, oxidative stress and cardiomyocyte apoptosis.

Figure 3. Relevance of CTRP12 to cardiovascular and metabolic diseases. Dysregulation of CTRP12 is closely related to the onset and development of cardiovascular and metabolic diseases. In particular, CTRP12 has a protective effect on CAD, heart failure, diabetes and NAFLD. However, CTRP12 plays a dual role in obesity progression, depending on the gender.

Figure 4. The role of CTRP12 in atherosclerosis. CTRP12 protects against the development of atherosclerosis through three pathways. Firstly, CTRP12 induces the polarization of macrophages toward a M2 phenotype to alleviate inflammatory response. Secondly, CTRP12 up-regulates the expression of ABCA1 and ABCG1 via the miR-155-5p/LXRα signaling cascade, leading to inhibition of macrophage foam cell formation. Thirdly, CTRP12 attenuates VSMC proliferation by activating the TGF-βRII/Smad2 axis.