Expression of matrix-degrading enzymes in pulmonary vascular remodeling in the rat.
Exposure of rats to hypoxia causes pulmonary arterial remodeling, which is partly reversible after return to air. We hypothesized that degradation of excess collagen in remodeled pulmonary arteries in the posthypoxic period is mediated by endogenous matrix metalloproteinases (MMPs). Total proteolytic, collagenolytic, and gelatinolytic activities, levels of stromelysin-1 and tissue inhibitor of metalloprotease-1 (TIMP-1), and immunolocalization of stromelysin-1 in main pulmonary arteries were determined after exposure of rats to 10% O2 for 10 days followed by normoxia. We observed transient increases in total proteolytic, collagenolytic, and gelatinolytic activities and expression of approximately 72-, 68-, and 60-kDa gelatinases by zymography within 3 days of cessation of hypoxic exposure. The level of TIMP-1 increased as the stromelysin-1 level increased. Immunoreactive stromelysin-1 was localized predominantly in the luminal region of normal and hypertensive pulmonary arteries. These results are consistent with the notion that endogenous MMPs may mediate the breakdown of excess collagen in remodeled pulmonary arteries during the early posthypoxic period.
Thakker-Varia
S
S
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.
Tozzi
C A
CA
Poiani
G J
GJ
Babiarz
J P
JP
Tatem
L
L
Wilson
F J
FJ
Riley
D J
DJ
D000818:Animals; D001160:Arterioles / Q000201:enzymology / Q000503:physiopathology; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D006168:Guinea Pigs; D006400:Hematocrit; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000503:physiopathology*; D000860:Hypoxia / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000201:enzymology* / Q000503:physiopathology; D051381:Rats; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3