[Effects of cigarette smoke exposure on pulmonary vascular intercellular adhesion molecule-1 and matrix metalloproteinase-9 in rats].
OBJECTIVE
To understand the effects of cigarette smoke exposure and smoke cessation on the structure, inflammation and remodeling of pulmonary blood vessels in rats.


METHODS
Thirty-two male Wistar rats were randomly divided into a control group, a smoke exposure group 1 (low dose smoke), a smoke exposure group 2 (high dose smoke) and a smoke cessation group, with 8 rats in each group. The ratio of pulmonary vascular wall thickness/vascular external diameter (WT%) and the ratio of pulmonary vascular wall area/total pulmonary vascular area (WA%) were measured by the image analysis system. The expressions of pulmonary vascular ICAM-1 and MMP-9 protein and mRNA were detected respectively by enzyme linked immunosorbent assay (ELISA) and in situ hybridization techniques.


RESULTS
WT% and WA% increased significantly in the smoke exposure group 1 [(15.3 +/- 2.1)%, (41 +/- 7)%] and smoke exposure group 2 [(18.0 +/- 2.0)%, (50 +/- 7)%] compared to those of the control group [(10.4 +/- 2.0)%, (30 +/- 4)%] (q = 4.93 - 11.16, P < 0.05, respectively). The WT% and WA% in the smoke cessation group [(11.0 +/- 1.3)%, (35 +/- 5)%] decreased significantly compared to those of the smoke exposure group 2 (q = 6.74 - 10.29, P < 0.05, respectively). The expression of pulmonary vascular ICAM-1 protein and mRNA increased significantly in the smoke cessation group, the smoke exposure group 1 and the smoke exposure group 2 [(7.9 +/- 3.2 and 6.2 +/- 3.0), (12.9 +/- 2.3 and 10.3 +/- 2.2), (19.2 +/- 2.3 and 18.3 +/- 2.4)] compared to those of the control group (4.7 +/- 2.3 and 2.7 +/- 1.7) (q = 3.28 - 15.76, P < 0.05, respectively). However, the expression of ICAM-1 protein and mRNA was lower in the smoke cessation group compared to those of the smoke exposure groups (q = 3.85 - 12.46, P < 0.05, respectively). The expression of MMP-9 protein and mRNA increased significantly in the smoke cessation group, smoke exposure group 1 and smoke exposure group 2 [(12.0 +/- 2.8 and 7.0 +/- 3.4), (16.1 +/- 2.8 and 12.5 +/- 1.8), (22.5 +/- 3.5 and 20.0 +/- 3.1)] compared to those of the control group (7.8 +/- 3.0 and 3.2 +/- 2.8) (q = 3.19 - 14.22, P < 0.05, respectively). But the expression of MMP-9 protein and mRNA was lower in the smoke cessation group compared to those of the smoke exposure groups (q = 3.68 - 11.03, P < 0.05, respectively). Both ICAM-1 and MMP-9 mRNA expression were positively correlated with WT% and WA% (r = 0.619 - 0.703) (P < 0.05, respectively).


CONCLUSIONS
Cigarette smoke exposure caused pulmonary vascular wall thickening. By up-regulating the expression of ICAM-1 and MMP-9 protein and mRNA in pulmonary vascular wall, cigarette smoke exposure mediated pulmonary vascular inflammation and remodeling, which were associated with pulmonary hypertension. Smoke cessation attenuated the smoke-induced pulmonary vascular impairment.
Hu
Xiao-Yun
XY
Department of Respiration Medicine, First Affiliate Hospital, Shanxi Medical University, Taiyuan 030001, China.
Zhang
Hong-Li
HL
Xu
Jian-Ying
JY
Wang
Chen
C
D000818:Animals; D004781:Environmental Exposure; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects
D012906:Smoke; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9