title: Bovine distal pulmonary arterial media is composed of a uniform population of well-differentiated smooth muscle cells with low proliferative capabilities.
abstract: The media of the normal bovine main pulmonary artery (MPA) is composed 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. With a panel of muscle-specific antibodies against alpha-smooth muscle (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 (1,500- to 100-microm diameter) is composed of a phenotypically uniform population of "well-differentiated" SMC. Similarly, when isolated and assessed in vitro, distal PA-SMC is composed of 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 composed 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 vs. proximal PA may confer different response mechanisms during remodeling in conditions such as hypertension.
authors.affiliation: Developmental Lung Biology Research, Univ. of Colorado Health Sciences Center, 4200 E. 9th Ave., Box B131, Denver, CO 80262, USA.
authors.forename: Leopold
authors.initials: L
authors.lastname: Stiebellehner
authors.forename: Maria G
authors.initials: MG
authors.lastname: Frid
authors.forename: John T
authors.initials: JT
authors.lastname: Reeves
authors.forename: Robert B
authors.initials: RB
authors.lastname: Low
authors.forename: Meena
authors.initials: M
authors.lastname: Gnanasekharan
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Stenmark
mesh_terms: D000818:Animals; D001790:Blood Physiological Phenomena; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010641:Phenotype; D014176:Protein Biosynthesis; D011651:Pulmonary Artery / Q000166:cytology* / Q000502:physiology; D017540:Tunica Media / Q000166:cytology* / Q000502:physiology