Gelatinase expression in pulmonary arteries during experimental pulmonary hypertension.
Structural remodelling of pulmonary vessels is an important feature of pulmonary hypertension (PH), which reflects distal artery muscularization and matrix remodelling. The matrix metalloproteinases (MMPs) are involved in extracellular matrix turnover and hence, in smooth muscle cell migration and endothelial cell migration and proliferation. Among the MMPs, gelatinases (MMP-2 and MMP-9) can degrade basement membrane components and promote cell proliferation and migration. This study evaluated gelatinases in pulmonary vessels during progressive PH in two rat models: exposure to hypoxia or monocrotaline. Zymography of tissue homogenates revealed an association of progression of hypoxic PH with a time-dependent increase in gelatinase MMP-2 activity, specific to pulmonary vessels. Increased MMP-2 activity was also found 30 days postmonocrotaline. Reverse transcription polymerase chain reaction demonstrated upregulation of MMP-2 messenger ribonucleic acid. Immunolocalization showed MMP-2 throughout the pulmonary vasculature, from the trunk to the distal vessels, with strong staining of the intima, media and adventitia. MMP-2 was found in its active form and gelatinolytic activity was correlated to PH severity. Activity localization by in situ zymography corroborated with the immunolocalization findings. In conclusion, the authors demonstrated that matrix metalloproteinase-2 activity is increased in pulmonary vessels during progression of pulmonary hypertension, probably as a result of involvement in the matrix turnover associated with vascular remodelling during pulmonary hypertension.
Frisdal
E
E
Unité INSERM U492, Faculté de Médecine de Créteil, France.
Gest
V
V
Vieillard-Baron
A
A
Levame
M
M
Lepetit
H
H
Eddahibi
S
S
Lafuma
C
C
Harf
A
A
Adnot
S
S
Dortho
M P
MP
D000818:Animals; D018450:Disease Progression; D006976:Hypertension, Pulmonary / Q000201:enzymology*; D000860:Hypoxia; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D023421:Models, Animal; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016686:Monocrotaline; D020778:Matrix Metalloproteinase 2