title: Endogenous hydrogen sulfide regulates pulmonary artery collagen remodeling in rats with high pulmonary blood flow.
abstract: 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.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West District, Beijing, 100034, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
authors.forename: Geng
authors.initials: G
authors.lastname: Bin
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
mesh_terms: 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
chemical_list: 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