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1 Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO, USA
2 Department of Molecular Physiology and Biophisics, University of Vermont, Burlington, VT, USA
* To whom correspondence should be addressed. E-mail: Maria.Frid{at}UCHSC.edu.
The media of the normal bovine main pulmonary artery (MPA) is comprised of phenotypically heterogeneous smooth muscle cells (SMC) with markedly different proliferative capabilities in response to serum, mitogens, and hypoxia. Little, however, is known of the SMC phenotype in distal pulmonary arteries (PA), particularly in arterioles, which regulate the pulmonary circulation. Using a panel of muscle-specific antibodies against 
-SM-actin, SM-myosin heavy chains (SM-MHC), SM-MHC-B isoform, desmin, and meta-vinculin, we demonstrate a progressive increase in phenotypic uniformity and level of differentiation of SMC along the proximal-to-distal axis of normal adult bovine pulmonary circulation, so that the media of distal PA (1500-to-100 µm diameter) is comprised of a phenotypically uniform population of ''well-differentiated'' SMC. Similarly, when isolated and assessed in vitro, distal PA-SMC comprised a single, uniform population of differentiated SMC that exhibited minimal growth responses to a variety of mitogens while their cell size increased substantially in response to serum. Their growth was inhibited by hypoxic exposure under all conditions tested. Distal PA-SMC also differed from MPA-SMC by exhibiting a distinct pattern of DNA synthesis in response to serum and mitogens. Thus, in contrast to the MPA, distal PA media is comprised of an apparently uniform population of well-differentiated SMC that are proliferation-resistant and have a substantial capacity to hypertrophy in response to growth-promoting stimuli. We thus speculate that distinct SMC phenotypes present in distal versus proximal PA may confer different response mechanisms during remodeling in conditions such as hypertension.
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