title: Recapitulation of developing artery muscularization in pulmonary hypertension.
abstract: Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 George Street, Room 773J, New Haven, CT 06511, USA.
authors.forename: Abdul Q
authors.initials: AQ
authors.lastname: Sheikh
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 George Street, Room 773J, New Haven, CT 06511, USA.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Lighthouse
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 George Street, Room 773J, New Haven, CT 06511, USA. Electronic address: daniel.greif@yale.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Greif
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*