Effects of basic fibroblast growth factor and cyclin D1 on cigarette smoke-induced pulmonary vascular remodeling in rats.

Sijing Zhou,Daxiong Zeng,Min Li,Gengyun Sun,Ran Wang,Junsheng Zhou

doi:10.3892/etm.2014.2044

Abstract

Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by resulting in pulmonary vascular remodeling that involves pulmonary artery smooth muscle cell proliferation. This study investigated the effects of basic fibroblast growth factor (bFGF) and cyclin D1 on the pulmonary vascular remodeling in smoking-exposed rats. Twenty-four male Wistar rats were randomly divided into four groups. Three tobacco-exposed groups were exposed to the smoke produced by 20 cigarettes for 60 min, twice a day for two, four or eight weeks, and the control group were exposed to fresh air. The expression of bFGF and cyclin D1 in the pulmonary arterial smooth muscle cells were determined using immunohistochemistry. Quantitative polymerase chain reaction was conducted to determine the expression levels of bFGF and cyclin D1 mRNA. In addition, the expression of bFGF and cyclin D1 proteins was evaluated by western blotting. The expression of bFGF and cyclin D1 at the mRNA and protein levels was shown to increase with the duration of smoke exposure (P<0.05). The correlation analysis indicated the expression of bFGF and cyclin D1 was positively associated with the pulmonary vessel wall thickness. The expression of bFGF was positively associated with that of cyclin D1. Collectively, the data demonstrated that the upregulation of bFGF and cyclin D1 occurred in rats subjected to smoke exposure, which may be associated with the abnormal proliferation of the smooth muscle cells in the pulmonary arteries.

Highlights

Introduction increased pulmonary vascular resistance and reduced elasticity
Pulmonary hypertension denotes a disorder of the pulmonary arterioles that is characterized by elevated pulmonary artery pressure, right‐heart failure, persistent vasoconstriction, thickening of the pulmonary vascular wall, vascular remodeling and a progressive increase of pulmonary vascular resistance [12,13]
The pathological foundation of pulmonary hypertension includes muscularization of the pulmonary arteries induced by the overproliferation and migration of pulmonary smooth muscle cells, intima‐media thickening of the arteriole and neointimal formation

Summary

Introduction

Introduction increased pulmonary vascular resistance and reduced elasticity. The overproliferation of pulmonary arterial smooth muscle cells is the predominant feature of pulmonary vascular remodeling, which induces thickening of the pulmonary arterial wall, stenosis of the lumina, and muscularization of the pulmonary arteries [2]. Previous studies [3,4] have indicated that cigarette smoke induces pulmonary vascular remodeling through direct affects on the lung vessels. Basic fibroblast growth factor (bFGF) has been reported to play an important role in the regulation of fibroblasts, airway smooth muscle cells, and endothelial cells through the autocrine and paracrine systems [5]. To the best of our knowledge, no study has been performed to investigate whether it is involved in the remodeling of lung vessels in rats exposed to cigarette smoke [6]. The aim was to investigate the effect of the duration of cigarette smoke exposure on the expression of bFGF and cyclin D1 in the pulmonary vessels in rats, based on which their roles in pulmonary vascular remodeling were investigated

Methods

Results

Conclusion