© 1997 American Heart Association, Inc.
Articles |
Smooth Muscle Cell Heterogeneity in Pulmonary and Systemic Vessels
Importance in Vascular Disease
From the Cardiovascular Pulmonary and Developmental Biology Research Laboratories, University of Colorado Health Sciences Center (M.G.F., E.C.D., A.G.D., K.R.S.), and the VA Medical Center (E.C.D.), Denver, Colo.
Correspondence to Kurt R. Stenmark, MD, Developmental Lung Biology Laboratory, University of Colorado Health Sciences Center, 4200 E 9th Ave, Box B131, Denver, CO 80262. E-mail kurt.stenmark{at}uchsc.edu
Abstract Experimental evidence is rapidly accumulating which demonstrates that the arterial media in both pulmonary and systemic vessels is not composed of a phenotypically homogeneous population of smooth muscle cells (SMCs) but rather of heterogeneous subpopulations of cells with unique developmental lineages. In vivo and in vitro observations strongly suggest that marked differences in the phenotype, growth, and matrix-producing capabilities of phenotypically distinct SMC subpopulations exist and that these differences are intrinsic to the cell type. These data also suggest that differential proliferative and matrix-producing capabilities of distinct SMC subpopulations govern, at least in part, the pattern of abnormal cell proliferation and matrix protein synthesis observed in the pathogenesis of vascular disease. Within the pulmonary circulation, the observation that the isolated medial SMC subpopulations exhibit differential proliferative responses to hypoxic exposure is important, since this in vitro cell-model system can now be used to better understand the mechanisms that regulate increased responsiveness of specific medial cell subpopulations to low oxygen concentrations. Our data also support the idea that protein kinase C is likely to be one important determinant of differential cell growth responses to hypoxia. The data also suggest differential involvement of specific arterial SMC subpopulations in the elastogenic responses of the vessel wall to injury. We believe that a better understanding of the mechanisms contributing to the unique behavior of specific arterial cell subpopulations will provide important future directions for therapies aimed at preventing abnormal cell replication and matrix protein synthesis in vascular disease.
Key Words: smooth muscle cell heterogeneity • protein kinase C • pulmonary hypertension • vascular remodeling • tropoelastin • proliferation • hypoxia
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