Objectives Retinol binding protein 4 (RBP4)-a newly discovered adipocytokines, has been found to be associated closely with obesity, insulin resistance, cardiac vascular disease (CVD), metabolic syndrome. Recent researches show that RBP4 levels may be used as biochemical markers of CVD in patients with type 2 diabetes. Abnormal proliferation and migration of vascular smooth muscle cell (VSMC) is one of the common foundation of atherosclerosis, vascular restenosis and other CVD. This study was conducted to decipher the relationship between RBP4 and VSMC proliferation in hyperinsulinismic rats model.
Methods Plasma RBP4, insulin resistance indexes and cardiovascular risk factors were measured from blood samples of hyperinsulinemic rats (HIns) and control SD rats (Cons). The vascular morphology and the expression of ERK1/2, P-ERK1/2 in arterial tissues of rats were assessed.
Results Weight, fasting plasma glucose (FPG), fasting insulin (FIns), homeostasis model assessment of insulin resistance (HOMA-IR), high sensitivity C reactive protein (hsCRP) and triglyceride were higher in HIns than those in Cons while high-density lipoproteincholesterol (HDL-C) in HIns was lower (P < 0.05). RBP4 is higher in HIns compared with Cons (P < 0.01). Media thickness (MT), lumen diameter (LD) of thoracic aorta in HIns were higher than those in Cons, but without statistical significance (P > 0.05). Both P-ERK1/2 protein and mRNA expression levels in thoracic aorta of HIns were significantly higher than that of Cons. Plasma RBP4 concentrations were positivly correlated with TG and hsCRP (r = 0.541, p = 0.046; r = 0.633. P = 0.015). While plasma RBP4 levels were positively correlated with MT and both P-ERK1/2 protein and mRNA expression levels (r = 0.910, p = 0.032; r = 0.880, P = 0.049; r = 0.895, p = 0.040). After adjustment for insulin level, RBP4 levels were still positively correlated with P-ERK1/2protein expression (r = 0.993, p = 0.007).
Conclusions Plasma RBP4 concentrations were significantly increased in Hyperinsulinemia SD rats, and circulating RBP4 levels were positively correlated with proliferation of rat aortic smooth muscle, and the phosphorylation of EPK1/2 signal pathway. These results suggest that RBP4 may mediates the proliferation of aortic smooth muscle in Hyperinsulinemia SD rats.