Association of serum phospholipid PUFAs with cardiometabolic risk: Beneficial effect of DHA on the suppression of vascular proliferation/inflammation

Abstract

OBJECTIVES: Blood or dietary polyunsaturated fatty acids (PUFAs), particularly ω3-PUFAs were known for cardiovascular protective effect. However, the results are still controversial. We aimed to investigate the association of serum phospholipid PUFAs with cardiometabolic risk through cross-sectional/experimental studies. DESIGN/METHODS: Serum phospholipid FA compositions and cardiometabolic risk parameters were measured in controls [healthy: n=987, metabolic syndrome (MetS): n=214] and CAD patients (CAD-only: n=152, CAD+MetS: n=56). Experimental assays were performed in vascular smooth muscle cells (VSMCs). RESULTS: Major cardiometabolic risk markers, i.e. insulin resistance, hs-C-reactive proteins, and malondialdehyde were higher, and adiponectin and LDL particle size were lower in CAD patients, particularly those with MetS than in healthy controls. Serum linoleic acid (LA, C18:2ω-6) was lowest and dihomo-γ-linolenic acids (DGLAs, C20:3ω-6) were highest in CAD patients with MetS among the 4 groups. Docosahexaenoic acid (DHA, C22:6ω-3) was lower and arachidonic acid (AA, C20:4ω-6) and ω6/ω3-PUFAs were higher in CAD patients than in controls. ω3-PUFAs were significantly lower in CAD patients, particularly those with MetS than in healthy controls. Multiple regression analysis revealed that AA and DHA among serum FAs were mainly associated with the cardiometabolic risk (β'-coefficients for AA:0.336; DHA: -0.296) together with age, MetS factors, LA, DGLA and gender (r=0.529, p<0.001). Under LPS-induced stress condition, LA and DHA significantly suppressed VSMC proliferation. DHA also up-regulated the phosphorylation of p38 and ERK, and dramatically inhibited nuclear translocation of NF-κB-p65 in VSMCs. CONCLUSION: AA and DHA were mainly associated with cardiometabolic risk. Particularly, DHA may be effective on suppression of vascular proliferation and inflammation.