title: Cyclic stretch affects pulmonary endothelial cell control of pulmonary smooth muscle cell growth.
abstract: Endothelial cells are subjected to mechanical forces in the form of cyclic stretch resulting from blood pulsatility. Pulmonary artery endothelial cells (PAECs) produce factors that stimulate and inhibit pulmonary artery smooth muscle cell (PASMC) growth. We hypothesized that PAECs exposed to cyclic stretch secrete proteins that inhibit PASMC growth. Media from PAECs exposed to cyclic stretch significantly inhibited PASMC growth in a time-dependent manner. Lyophilized material isolated from stretched PAEC-conditioned media significantly inhibited PASMC growth in a dose-dependent manner. This inhibition was reversed by trypsin inactivation, which is consistent with the relevant factor being a protein(s). To identify proteins that inhibited cell growth in conditioned media from stretched PAECs, we used proteomic techniques and found that thrombospondin (TSP)-1, a natural antiangiogenic factor, was up-regulated by stretch. In vitro, exogenous TSP-1 inhibited PASMC growth. TSP-1-blocking antibodies reversed conditioned media-induced inhibition of PASMC growth. Cyclic stretched PAECs secrete protein(s) that inhibit PASMC proliferation. TSP-1 may be, at least in part, responsible for this inhibition. The complete identification and understanding of the secreted proteome of stretched PAECs may lead to new insights into the pathophysiology of pulmonary vascular remodeling.
authors.affiliation: Pulmonary and Critical Care Unit, Massachusetts General Hospital, Bullfinch 148, 55 Fruit Street, Boston, MA 02114, USA. cdo701@jaguar1.usouthal.edu
authors.forename: Cristhiaan D
authors.initials: CD
authors.lastname: Ochoa
authors.forename: Haven
authors.initials: H
authors.lastname: Baker
authors.forename: Stephen
authors.initials: S
authors.lastname: Hasak
authors.forename: Robina
authors.initials: R
authors.lastname: Matyal
authors.forename: Aleya
authors.initials: A
authors.lastname: Salam
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hales
authors.forename: William
authors.initials: W
authors.lastname: Hancock
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Quinn
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D015925:Cryopreservation; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000502:physiology; D006706:Homeostasis; D009130:Muscle, Smooth / Q000166:cytology* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000166:cytology / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000199:Actins; D017077:Culture Media, Conditioned; D014841:von Willebrand Factor