Site-specific Responses to Monocrotaline-induced Vascular Injury: Evidence for Two Distinct Mechanisms of Remodeling

Yoshihiro Tanaka, Matthew L. Bernstein, Robert P. Mecham, G. Alexander Patterson, Joel D. Cooper, Mitchell D. Botney

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Monocrotaline (MCT)-induced pulmonary vascular injury was used to begin studying the mechanism(s) of vascular remodeling in Fischer 344 rats, using extracellular matrix (ECM) gene expression to define areas of remodeling. By day 28 after injection, pulmonary artery pressures were increased and right ventricular hypertrophy had developed compared with normal controls. Tropoelastin, fibronectin, and α1(I) procollagen mRNA levels increased at least 2-fold by day 28. In situ hybridization demonstrated tropoelastin gene expression by cells adjacent to the lumen and procollagen gene expression at the medialadventitial border in both small muscular and large elastic pulmonary arteries. This pattern of gene expression was observed as early as 1 wk after MCT injury. These observations indicated two distinct areas of remodeling, one along the vascular lumen at the site of monocrotaline-induced injury and the other at a second distinct site. To determine whether other differences may be involved at these two sites, the presence of transforming growth factor-β (TGF-β) was studied. Total TGF-β protein was 4-fold higher in remodeling lungs compared with normal lungs. Gene expression for all three isoforms of TGF-β colocalized with tropoelastin gene expression along the vascular lumen but not with α1(I) procollagen gene expression. These results suggest a complex site-specific response to injury mediated by two distinct pathways in this model of pulmonary vascular remodeling.

Original languageEnglish
Pages (from-to)390-397
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume15
Issue number3
DOIs
StatePublished - Jan 1 1996

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