SMOOTH-MUSCLE CELL HETEROGENEITY IN PULMONARY AND SYSTEMIC VESSELS - IMPORTANCE IN VASCULAR-DISEASE

Experimental evidence is rapidly accumulating which demonstrates that the arterial media in both pulmonary and systemic vessels is not compo sed 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 su ggest that marked differences in the phenotype, growth, and matrix-pro ducing capabilities of phenotypically distinct SMC subpopulations exis t and that these differences are intrinsic to the cell type. These dat a also suggest that differential proliferative and matrix-producing ca pabilities of distinct SMC subpopulations govern, at least in part, th e 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 subpopulati ons exhibit differential proliferative responses to hypoxic exposure i s important, since this in vitro cell-model system can now be used to better understand the mechanisms that regulate increased responsivenes s of specific medial cell subpopulations to low oxygen concentrations. Our data also support the idea that protein kinase C is likely to Se one important determinant of differential cell growth responses to hyp oxia. The data also suggest differential involvement of specific arter ial SMC subpopulations in the elastogenic responses of the vessel wall to injury. We believe that a better understanding of the mechanisms c ontributing to the unique behavior of specific arterial cell subpopula tions will provide important future directions for therapies aimed at preventing abnormal cell replication and matrix protein synthesis in v ascular disease.