Autocrine Human Urotensin II Enhances Macrophage-Derived Foam Cell Formation in Transgenic Rabbits.

Enqi Liu,Shoucui Gao,Jianglin Fan,Lijing Sun,Daxing Cheng,Hua Guan,Xiaojing Wang,Rong Wang,Sihai Zhao,Yafeng Li,Liang Bai

doi:10.1155/2015/843959

Enqi Liu, Shoucui Gao + Show 9 more

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https://doi.org/10.1155/2015/843959

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Abstract

Circulating urotensin II (UII) is involved in the development of atherosclerosis. However, the role of autocrine UII in the development of atherosclerosis remains unclear. Here, we tested the hypothesis that autocrine UII would promote atherosclerosis. Transgenic rabbits were created as a model to study macrophage-specific expressing human UII (hUII) and used to investigate the role of autocrine UII in the development of atherosclerosis. Transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet to induce atherosclerosis. Comparing the transgenic rabbits with their nontransgenic littermates, it was observed that hUII expression increased the macrophage-positive area in the atherosclerotic lesions by 45% and the positive area ratio by 56% in the transgenic rabbits. Autocrine hUII significantly decreased the smooth muscle cell-positive area ratio in transgenic rabbits (by 54%), without affecting the plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glucose and adipose tissue contents. These results elucidated for the first time that autocrine UII plays an important role in the development of atherosclerosis by increasing the accumulation of macrophage-derived foam cell.

Highlights

Atherosclerotic cardiovascular diseases, including heart attack, stroke, and peripheral vascular insufficiency, continue to be the principal cause of death and disability in the world
A total of 769 zygotes of rabbits were microinjected with fragmented human UII (hUII) cDNA, and 40 pups were born
The real-time polymerase chain reaction (PCR) analysis showed that the hUII transgene in the transgenic rabbits was predominantly expressed in the isolated macrophages and less expressed in the aorta and macrophage-rich tissues (Figure 1(c))

Summary

Introduction

Atherosclerotic cardiovascular diseases, including heart attack, stroke, and peripheral vascular insufficiency, continue to be the principal cause of death and disability in the world. Vasoactive peptides play an important role in the development of atherosclerosis [1]. Circulating UII increases plasma reactive oxygen species (ROS) and oxidized low-density lipoprotein (ox-LDL) and upregulates the expression of vascular cell adhesion protein (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), scavenger receptors (CD36 and scavenger receptor class A), and acyl-CoA, which are important molecules in the initiation and progression stages of atherosclerosis lesion formation [8,9,10]. Whether autocrine UII plays an important role in the development of atherosclerosis remains unclear. We created transgenic rabbits to investigate the role of autocrine UII in the development of atherosclerosis by the macrophage-specific expression of human UII.

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