The role of Leptin in vascular remodeling induced by partial ligation of portal vein in rats

Abstract

Background and aims: Hypertension poses major risks for cardiovascular diseases. Vascular remodeling in hypertension plays a crucial role in precipitating these complications and in maintaining the elevated blood pressure. Remodeling is believed to be a consequence of altered forces exerted on the vessel wall as a result of hypertension, as well as hormonal influences on the vascular smooth muscle cells (VSMCs) of these blood vessels. VSMCs in small resistance vessels are important regulators of total peripheral resistance and are known to play an important role in the process of vascular remodeling in hypertension. Obesity is known to be associated with hypertension, and this is accompanied by high levels of leptin and low levels of adiponectin, changes that have been linked to cardiovascular complications. Leptin and adiponectin are expressed by VSMCs. Leptin mediates the stretch-induced vascular hypertrophy in the rat portal vein (RPV). In contrast, hypoadiponectinemia is considered an independent risk factor for hypertension. This study aimed at further exploring the role of leptin and adiponectin in vascular remodeling induced by increased intravascular pressure, in vivo, using the partial portal vein ligated model (PVL) of portal hypertension in rats, and in vitro using mechanical stretch of the isolated RPV. We examined the effect of these two models on expression and levels of leptin and adiponectin and on transduction mechanisms associated with leptin and vascular remodeling including STAT-3 and reactive oxygen species (ROS).As well as we studied the effect of leptin on the transcription factor NFKBp65 nuclear translocation. Methods: Partial ligation of the RPV or sham operation were conducted and portal veins were studied on days 2,7 or 14 after surgery to examine the effect of increased transmural pressure. In a separate group of rats the portal veins were isolated and subjected to mechanical stretch. An immunometric assay was used to quantify leptin plasma concentrations. Western Blotting analysis