MAST-CELL COLLAGENASE CORRELATES WITH REGRESSION OF PULMONARY VASCULAR REMODELING IN THE RAT

Pulmonary vascular remodeling, produced by cell hypertrophy and extrac ellular matrix protein synthesis in response to hemodynamic stress, re gresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and el astase in pulmonary arteries of rats exposed to hypoxia (10% O-2 for 1 0 d) followed by normoxia. During hypoxia, contents of collagen and el astin increased in pulmonary arteries and latent rat interstitial coll agenase was expressed without increased collagenolytic activity or mRN A levels. At 3 days after normoxia, collagen and elastin contents decr eased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in conne ctive tissue-type mast cells, was increased in the adventitia and medi a of hypertensive vessels. We conclude that mast cells containing late nt collagenase are recruited into the outer walls of pulmonary arterie s during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular arch itecture.