Effects of MMP-1 and MMP-7 on Pulmonary Hypertension in Rats

Ruyi FANG; Honglu LIU; Haiwen LI; Xi CHENG; Yangjun CHEN; Yushan LI; Yongrui YANG; Nihong LU

doi:10.12259/j.issn.2095-610X.S20230305

Volume 44 Issue 3

Mar. 2023

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Ruyi FANG, Honglu LIU, Haiwen LI, Xi CHENG, Yangjun CHEN, Yushan LI, Yongrui YANG, Nihong LU. Effects of MMP-1 and MMP-7 on Pulmonary Hypertension in Rats[J]. Journal of Kunming Medical University, 2023, 44(3): 34-43. doi: 10.12259/j.issn.2095-610X.S20230305

Citation:

Ruyi FANG, Honglu LIU, Haiwen LI, Xi CHENG, Yangjun CHEN, Yushan LI, Yongrui YANG, Nihong LU. Effects of MMP-1 and MMP-7 on Pulmonary Hypertension in Rats[J]. Journal of Kunming Medical University, 2023, 44(3): 34-43. doi: 10.12259/j.issn.2095-610X.S20230305

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Effects of MMP-1 and MMP-7 on Pulmonary Hypertension in Rats

doi: 10.12259/j.issn.2095-610X.S20230305

1.
Dept. of Respiratory and Critical Care Medicine
2.
Dept. of Science and Education，Kunming Third People’s Hospital，Kunming Yunnan 650041
3.
Dept. of Pain，Yunnan Provincial Hospital of Traditional Chinese Medicine，Kunming Yunnan 650021，China

Received Date: 2022-12-07
Available Online: 2023-03-08
Publish Date: 2023-03-25

Abstract

Abstract

Objective To explore the effects of MMP-1 and MMP-7 on pulmonary arterial hypertension （PAH）. Methods The contents of MMPs （MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, MMP-14） in the serum of PAH patients and healthy controls were detected and two MMPs were selected for in vivo experiments. Clinical information was collected and body mass index （BMI）, NYHA cardiac function class, 6 min walking distance （6MWD）, brain natriuretic peptide （BNP）, mean pulmonary arterial pressure （mPAP）, triglyceride （TGs）, low-density lipoprotein （LDL）, total cholesterol （TC）, hemoglobin （HB）, heart rate （HR） were compared between PAH patients and healthy controls. The PAH rat model was induced by monocrotaline, and then MMP-1 overexpression plasmid and shMMP-7 plasmid were used to up-regulate and down-regulate the expression of MMP-1 and MMP-7, respectively. Hematoxylin-eosin （HE） staining was used to observe the pathological of PAH, Masson staining was used to observe the changes of muscle fibers and collagen fibers, and immunofluorescence was used to detect the expression of α-SMA and VWF. The left ventricle, right ventricle and interventricular septum were weighed and the right ventricular hypertrophy index was calculated. Results The serum levels of MMP-1 （P < 0.0001）, MMP-2 （P < 0.001）, MMP-7 （P < 0.01）, MMP-9 （P < 0.001）, MMP-10 （P < 0.001） and MMP-14 （P < 0.01） in PAH patients were significantly higher than those in healthy controls. 6MWD was significantly decreased （P < 0.05）, BNP level was increased （P < 0.001）, NYHA class was increased （P < 0.0001）. Compared with the control group, the protein expression of MMP-1 （P < 0.0001） and MMP-7 （P < 0.0001） in lung tissue, right ventricular hypertrophy index （P < 0.0001）, pulmonary artery vascular thickness （P < 0.05）, and collagen fiber deposition （P < 0.05） were increased in PAH rats. The expressions of α-SMA （P < 0.05） and VWF （P < 0.05） in blood vessels were increased in PAH rats than control rats. Compared with PAH group, overexpression of MMP-1 in PAH rats promoted the development of PAH, while interference with MMP-7 delayed its development. Conclusions The serum levels of MMPs （MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, MMP-14） are increased in patients with PAH. MMP-1 and MMP-7 promote pulmonary artery remodeling, pulmonary fibrosis and right ventricular dysfunction in PAH rats.
- MMP-1,
- MMP-7,
- Pulmonary arterial hypertension

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References(34)

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