Endogenous hydrogen sulfide regulates pulmonary artery collagen remodeling in rats with high pulmonary blood flow.
The mechanisms responsible for the structural remodeling of pulmonary vasculature induced by increased pulmonary blood flow are not fully understood. This study explores the effect of endogenous hydrogen sulfide (H2S), a novel gasotransmitter, on collagen remodeling of the pulmonary artery in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into sham, shunt, sham+PPG (D,L-propargylglycine, an inhibitor of cystathionine-gamma-lyase), and shunt+PPG groups. After 4 weeks of shunting, the relative medial thickness (RMT) of pulmonary arteries and H2S concentration in lung tissues were investigated. Collagen I and collagen III were evaluated by hydroxyproline assay, sirius-red staining, and immunohistochemistry. Pulmonary artery matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 4 weeks of aortocaval shunting, resulting in an elevation of lung tissue H2S to 116.4%, rats exhibited collagen remodeling and increased CTGF expression in the pulmonary arteries. Compared with those of the shunt group, lung tissue H2S production was lowered by 23.4%, RMT of the pulmonary artery further increased by 39.5%, pulmonary artery collagen accumulation became obvious, and pulmonary artery CTGF expression elevated (P<0.01) in the shunted rats treated with PPG. However, pulmonary artery MMP-13 and TIMP-1 expressions decreased significantly in rats of shunt+PPG group (P<0.01). This study suggests that endogenous H2S exerts an important regulatory effect on pulmonary collagen remodeling induced by high pulmonary blood flow.
Li
Xiaohui
X
Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West District, Beijing, 100034, People's Republic of China.
Jin
Hongfang
H
Bin
Geng
G
Wang
Li
L
Tang
Chaoshu
C
Du
Junbao
J
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006330:Heart Defects, Congenital / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D011651:Pulmonary Artery / Q000378:metabolism* / Q000503:physiopathology; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D000480:Alkynes; C526316:CCN2 protein, rat; D024042:Collagen Type I; D024061:Collagen Type III; D004791:Enzyme Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D055513:Connective Tissue Growth Factor; C009055:propargylglycine; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide