ENDOTHELIAL-CELL EXPRESSION OF VASOCONSTRICTORS AND GROWTH-FACTORS ISREGULATED BY SMOOTH-MUSCLE CELL-DERIVED CARBON-MONOXIDE

Citation
T. Morita et S. Kourembanas, ENDOTHELIAL-CELL EXPRESSION OF VASOCONSTRICTORS AND GROWTH-FACTORS ISREGULATED BY SMOOTH-MUSCLE CELL-DERIVED CARBON-MONOXIDE, The Journal of clinical investigation, 96(6), 1995, pp. 2676-2682
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
96
Issue
6
Year of publication
1995
Pages
2676 - 2682
Database
ISI
SICI code
0021-9738(1995)96:6<2676:EEOVAG>2.0.ZU;2-A
Abstract
CO is produced in vascular smooth muscle cells (VSMC) by heme oxygenas e-1 (HO-1). CO increases cGMP levels in VSM; however, its possible add itional roles in the vasculature have not been examined, We report tha t a product of HO, released from VSMC and inhibited by hemoglobin, has paracrine effects on endothelial cells: it increases endothelial cGMP content and decreases the expression of the mitogens, endothelin-1 (E T-1) and platelet-derived growth factor-E (PDGF-B). This product has t he characteristics of CO, and its production is increased sevenfold un der hypoxia, The VSMC-derived CO caused a fourfold rise in endothelial cell cGMP, In addition, it inhibited the hypoxia-induced increases in mRNA levels of the ET-1 and PDGP-B genes, Inhibitors of HO, and hemog lobin, a scavenger of CO, prevented the rise in cGMP and also restored the hypoxic response of these genes, The inhibition of ET-1 and PDGF- B mRNA by CO resulted in decreased production of these endothelial-der ived mitogens, and in turn, inhibition of VSMC proliferation, These fi ndings suggest an important physiologic role for VSMC-derived CO in mo dulating cell-cell interaction and cell proliferation in the vessel wa ll during hypoxia.