» Articles » PMID: 15863640

Smooth Muscle Cell Matrix Metalloproteinases in Idiopathic Pulmonary Arterial Hypertension

Overview
Journal Eur Respir J
Specialty Pulmonary Medicine
Date 2005 May 3
PMID 15863640
Citations 65
Authors
Affiliations
Soon will be listed here.
Abstract

Pulmonary arterial hypertension (PAH) results from persistent vasoconstriction, smooth muscle growth and extracellular matrix (ECM) remodelling of pulmonary arteries (PAs). Matrix metalloproteinases (MMPs) are matrix-degrading enzymes involved in ECM turnover, and in smooth muscle cell (SMC) and endothelial cell migration and proliferation. MMP expression and activity are increased in experimental PAH. Therefore, this study investigated whether similar changes occur in idiopathic PAH (IPAH; formerly known as primary pulmonary hypertension). Both in situ and in vitro studies were performed on PAs from patients undergoing lung transplantation for IPAH and from patients treated by lobectomy for localised lung cancer, who served as controls. In IPAH, MMP-tissue inhibitor of metalloproteinase (TIMP) imbalance was found in cultured PA-SMCs, with increased TIMP-1 and decreased MMP-3. MMP-2 activity was markedly elevated as a result of increases in both total MMP-2 and proportion of active MMP-2. In situ zymography and immunolocalisation showed that MMP-2 was associated with SMCs and elastic fibres, and also confirmed the MMP-3-TIMP-1 imbalance. In conclusion, the findings of this study were consistent with a role for the matrix metalloproteinase-tissue inhibitor of metalloproteinase system in pulmonary vascular remodelling in idiopathic pulmonary arterial hypertension. The matrix metalloproteinase-tissue inhibitor of metalloproteinase imbalance may lead to matrix accumulation, and increased matrix metalloproteinase-2 activity may contribute to smooth muscle cell migration and proliferation. Whether these abnormalities are potential therapeutic targets deserves further investigation.

Citing Articles

Crocin's role in modulating MMP2/TIMP1 and mitigating hypoxia-induced pulmonary hypertension in mice.

Deng J, Wei R, Zhang W, Shi C, Yang R, Jin M Sci Rep. 2024; 14(1):12716.

PMID: 38830933 PMC: 11148111. DOI: 10.1038/s41598-024-62900-8.


Effect of Qiling Jiaogulan Powder on Pulmonary Fibrosis and Pulmonary Arteriole Remodeling in Low-Temperature-Exposed Broilers.

Yu J, Li P, Duan Z, Liu X Animals (Basel). 2023; 13(1).

PMID: 36611616 PMC: 9817788. DOI: 10.3390/ani13010005.


Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters.

Jasenovec T, Radosinska D, Kollarova M, Vrbjar N, Balis P, Trubacova S Pharmaceuticals (Basel). 2022; 15(10).

PMID: 36297339 PMC: 9611329. DOI: 10.3390/ph15101227.


Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening.

Liu S, Nambiar Veetil N, Li Q, Kucherenko M, Knosalla C, Kuebler W Front Immunol. 2022; 13:959209.

PMID: 36275740 PMC: 9579293. DOI: 10.3389/fimmu.2022.959209.


Plasma matrix metalloproteinase 2 is associated with severity and mortality in pulmonary arterial hypertension.

Arvidsson M, Ahmed A, Saleby J, Hesselstrand R, Radegran G Pulm Circ. 2022; 12(1):e12041.

PMID: 35506077 PMC: 9053005. DOI: 10.1002/pul2.12041.