Vascular remodeling in neonatal pulmonary hypertension. Role of the smooth muscle cell.
We suggest that hypoxia-induced pulmonary hypertension in the newborn calf is an attractive model for studying the mechanisms underlying alterations in extracellular matrix accumulation which occur in pulmonary vascular disease. Our data support a model (Fig 7) in which the SMC, perhaps as a result of hypoxic and/or pressure-induced vessel wall injury, becomes phenotypically altered. This phenotypically altered SMC generates a factor, termed smooth muscle derived extracellular matrix factor (SMEF), and possibly other factors. SMEF, in turn, stimulates or induces elastin and collagen synthesis in fibroblasts and endothelial cells. SMEF, or an associated activity derived from phenotypically altered smooth muscle cells, also induces elastin receptor expression on the cell surface and affects the chemotactic responsiveness of vascular cells. Thus, the SMC may be able to affect both the secretory and responsive properties of cell types in the vascular wall. The SMC may be critical in the vascular remodeling in pulmonary hypertension. The possible autocrine or paracrine alteration of cellular phenotypes by smooth muscle-derived mediators provides an important new direction for future research into molecular and cellular mechanisms of connective tissue regulation in diseased vessels.
Stenmark
K R
KR
University of Colorado Health Sciences Center, Cardiovascular Laboratory, Denver.
Orton
E C
EC
Reeves
J T
JT
Voelkel
N F
NF
Crouch
E C
EC
Parks
W C
WC
Mecham
R P
RP
D000531:Altitude; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D002418:Cattle Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D004549:Elastin / Q000096:biosynthesis; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology
D003094:Collagen; D004549:Elastin