PDGF and microvessel wall remodeling in adult lung: imaging PDGF-Rbeta and PDGF-BB molecules in progenitor smooth muscle cells developing in pulmonary hypertension.
Smooth muscle cells are relatively rare cells in the microvessels of the normal adult lung but develop in high numbers in the clinical pulmonary hypertensions (PHs). Understanding this cellular response has profound implications for determining the pathogenesis of PH, and for the development of therapeutic strategies, yet little is known of the angiogenic molecules responsible. The authors have previously shown that interstitial fibroblasts, and intermediate cells, are the progenitors of smooth muscle cells developing in adult lung microvessels in an in vivo model of experimental PH. The present study evaluates PDGF-Rbeta/PDGF-BB, an important angiogenic signaling pathway, using antibodies linked to protein A-gold (pA-AU) and quantitative high-resolution imaging techniques to detect expression by these cells. Each progenitor cell type in the control lung expressed PDGF-Rbeta and PDGF-BB. In the hypertensive lung, PDGF-Rbeta was highly expressed by fibroblasts developing as perivascular cells, the mean number of pA-AU labeled antigenic sites per cell profile, and their density (microm(-2)), increasing with time: in intermediate cells the mean number of sites per cell profile, although not their density (microm(-2)), also increased with time but less so than in the fibroblasts. In clear contrast to the RTK, constitutive expression levels of PDGF-BB were low in each progenitor cell type and remained restricted in the hypertensive lung.
Jones
Rosemary
R
Department of Anesthesia and Critical Care, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts 02129, USA. jones@etherdome.mgh.harvard.edu
Capen
Diane
D
Jacobson
Margaretha
M
D000818:Animals; D000077214:Becaplermin; D001808:Blood Vessels / Q000503:physiopathology; D005347:Fibroblasts / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta