Effect of hepatocyte growth factor on mice with hypoxic pulmonary arterial hypertension: a preliminary study
TANG Hu-Ting, MU Wei-Hao, XIANG Yu-Jing, AN Yong
Department of Cardiovascular and Thoracic Surgery, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China
Abstract Objective To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH. Methods After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery. Results Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (P<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (P<0.05). Conclusions Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.
Corresponding Authors:
An Y, Email: incavnate@126.com
E-mail: incavnate@126.com
Cite this article:
TANG Hu-Ting,MU Wei-Hao,XIANG Yu-Jing et al. Effect of hepatocyte growth factor on mice with hypoxic pulmonary arterial hypertension: a preliminary study[J]. CJCP, 2022, 24(8): 936-941.
TANG Hu-Ting,MU Wei-Hao,XIANG Yu-Jing et al. Effect of hepatocyte growth factor on mice with hypoxic pulmonary arterial hypertension: a preliminary study[J]. CJCP, 2022, 24(8): 936-941.
Radik M, Kmecova Z, Veteskova J, et al. Hepatocyte growth factor plays a particular role in progression of overall cardiac damage in experimental pulmonary hypertension[J]. Int J Med Sci, 2019, 16(6): 854-863. PMID: 31337959. PMCID: PMC6643116. DOI: 10.7150/ijms.31690.
Naito A, Sakao S, Lang IM, et al. Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor[J]. BMC Pulm Med, 2018, 18(1): 197. PMID: 30594174. PMCID: PMC6310963. DOI: 10.1186/s12890-018-0769-3.
Li T, Li S, Feng Y, et al. Combination of dichloroacetate and atorvastatin regulates excessive proliferation and oxidative stress in pulmonary arterial hypertension development via p38 signaling[J]. Oxid Med Cell Longev, 2020, 2020: 6973636. PMID: 32617141. PMCID: PMC7306075. DOI: 10.1155/2020/6973636.
Chu T, Huang M, Zhao Z, et al. Atorvastatin reduces accumulation of vascular smooth muscle cells to inhibit intimal hyperplasia via p38 MAPK pathway inhibition in a rat model of vein graft[J]. Arq Bras Cardiol, 2020, 115(4): 630-636. PMID: 33111860. PMCID: PMC8386959. DOI: 10.36660/abc.20190231.
Pang Y, Liang MT, Gong Y, et al. HGF reduces disease severity and inflammation by attenuating the NF-κB signaling in a rat model of pulmonary artery hypertension[J]. Inflammation, 2018, 41(3): 924-931. PMID: 29442198. DOI: 10.1007/s10753-018-0747-1.
Tahara Y, Ido A, Yamamoto S, et al. Hepatocyte growth factor facilitates colonic mucosal repair in experimental ulcerative colitis in rats[J]. J Pharmacol Exp Ther, 2003, 307(1): 146-151. PMID: 12954797. DOI: 10.1124/jpet.103.054106.
Yin Y, Guo J, Teng F, et al. Preparation of a novel one-armed anti-c-met antibody with antitumor activity against hepatocellular carcinoma[J]. Drug Des DevelTher, 2019, 13: 4173-4184. PMID: 31849449. PMCID: PMC6911325. DOI: 10.2147/DDDT.S224491.
Pan J, Li K, Huang W, et al. MiR-137 inhibited cell proliferation and migration of vascular smooth muscle cells via targeting IGFBP-5 and modulating the mTOR/STAT3 signaling[J]. PLoS One, 2017, 12(10): e0186245. PMID: 29016699. PMCID: PMC5634643. DOI: 10.1371/journal.pone.0186245.
Huang TX, Guan XY, Fu L. Therapeutic targeting of the crosstalk between cancer-associated fibroblasts and cancer stem cells[J]. Am J Cancer Res, 2019, 9(9): 1889-1904. PMID: 31598393. PMCID: PMC6780671.