Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE -/- Mice.

Background: Vascular remodeling is the most critical pathogenesis of atherosclerosis. Adipokine chemerin was known for its relationship with obesity as well as metabolism. Most recently, chemerin was found to play a crucial role in the pathologic process of cardiovascular diseases including coronary heart disease. In this study, we surveyed the role of chemerin in progression of atherosclerosis in ApoE-/- mice.

Objective: To investigate the relationship between chemerin and progression of atherosclerosis in ApoE-/- mice and its mechanism.

Methods: 8-week-old ApoE-/- mice were fed with high-fat diet to induce the atherosclerosis model. Adenoviruses were transfected for knockdown or overexpression of chemerin gene into aorta. Serums and aortic tissues of ApoE-/- mice were obtained after feeding high-fat diet for 16 weeks. HE staining and oil red staining were performed to evaluate aortic plaque. ELISA was performed to explore serum levels of tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), and transforming growth factor- β 1 (TGF- β 1). Real-time PCR and western blotting were carried out to investigate the mRNA and protein levels of chemerin, nuclear factor- κ B p65 (NF- κ Bp65), proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase ( p -p38-MAPK), phosphorylated c-Jun N-terminal kinase ( p -JNK), and phosphorylated extracellular signal regulated kinase 1/2 ( p -ERK 1/2).

Result: Aortic plaque formation was significantly induced by high-fat diet in ApoE-/- mice. Simultaneously, elevated serum levels of TNF- α and IL-1 β and elevated mRNA and protein levels of chemerin, NF- κ Bp65, PCNA, p -p38-MAPK, p -JNK, and p -ERK 1/2 were found in ApoE-/- mice. After aortic chemerin gene was inhibited by adenovirus, aortic atherosclerosis induced by high-fat diet was significantly meliorated, serum levels of TNF- α and IL-1 β decreased, mRNA and protein levels of NF- κ Bp65, PCNA, p -p38-MAPK, p -JNK, and p -ERK 1/2 decreased simultaneously.

Conclusion: Our study revealed that chemerin stimulated the progression of atherosclerosis in ApoE-/- mice.