1: Arterioscler Thromb Vasc Biol. 1999 Nov;19(11):2666-72. 

Platelet-derived growth factor stimulates heme oxygenase-1 gene expression and
carbon monoxide production in vascular smooth muscle cells.

Durante W, Peyton KJ, Schafer AI.

Houston VA Medical Center, Department of Medicine, Baylor College of Medicine,
Houston, TX 77030, USA. wdurante@bcm.tmc.edu

Recent studies indicate that vascular smooth muscle cells (VSMCs) generate CO
from the degradation of heme by the enzyme heme oxygenase-1 (HO-1). Because
platelet-derived growth factor (PDGF) modulates various responses of VSMCs, we
examined whether this peptide regulates the expression of HO-1 and the
production of CO by rat aortic SMCs. Treatment of SMCs with PDGF resulted in a
time- and concentration-dependent increase in the levels of HO-1 mRNA and
protein. Both actinomycin D and cycloheximide blocked PDGF-stimulated HO-1 mRNA
and protein. In addition, PDGF stimulated the production of reactive oxygen
species by SMCs. Both the PDGF-mediated generation of reactive oxygen species
and the induction of HO-1 protein was inhibited by the antioxidant
N-acetyl-L-cysteine. Incubation of platelets with PDGF-treated SMCs resulted in
a significant increase in platelet cGMP concentration that was reversed by
treatment of SMCs with the HO-1 inhibitor tin protoporphyrin-IX or by addition
of the CO scavenger hemoglobin to platelets. In contrast, the nitric oxide
inhibitor methyl-L-arginine did not block the stimulatory effect of PDGF-treated
SMCs on platelet cGMP. Finally, incubation of SMCs with the releasate from
collagen-activated platelets induced HO-1 protein expression that was blocked by
a neutralizing antibody to PDGF. These results demonstrate that either
administered exogenously or released by platelets, PDGF stimulates HO-1 gene
expression and CO synthesis in vascular smooth muscle. The ability of PDGF to
induce HO-1-catalyzed CO release by VSMCs may represent a novel mechanism by
which this growth factor regulates vascular cell and platelet function.

PMID: 10559009 [PubMed - indexed for MEDLINE]