title: Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent.
abstract: To maintain normal blood flow, pressure overload in both arteries and veins requires a structural adaptation of the vessel wall (remodelling) that involves smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely candidate to initiate and/or promote remodelling in blood vessels exposed to a chronic increase in blood pressure. To test this hypothesis, isolated segments of the rabbit carotid artery and jugular vein were perfused at different levels of intraluminal pressure. In both types of segments, pressure overload (160 and 20 mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the media was observed, while in the vein medial SMC started to proliferate. Isolated SMC from these rabbit blood vessels as well as from the aorta and vena cava of the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB-R-mediated increase in apoptosis upon exposure to mechanical deformation plus exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the cultured SMC did not respond with an increase in apoptosis under otherwise identical experimental conditions. These findings suggest that deformation-induced activation of the endothelin system in the vessel wall not only plays a crucial role in remodelling, but that the structural components of the vessel wall, in particular the cell-matrix interaction, determine how SMC respond phenotypically to these changes in gene expression.
authors.affiliation: Department of Cardiovascular Physiology, University of Goettingen, Humboldtallee 23, 37073 Goettingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Cattaruzza
authors.forename: M M
authors.initials: MM
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Ochs
authors.forename: A
authors.initials: A
authors.lastname: Fayyazi
authors.forename: L
authors.initials: L
authors.lastname: Füzesi
authors.forename: J
authors.initials: J
authors.lastname: Richter
authors.forename: M
authors.initials: M
authors.lastname: Hecker
mesh_terms: D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000378:metabolism / Q000648:ultrastructure; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002843:Chromatin / Q000648:ultrastructure; D046508:Culture Techniques; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011312:Pressure; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics / Q000502:physiology*; D013314:Stress, Mechanical; D014680:Veins / Q000648:ultrastructure
chemical_list: D002843:Chromatin; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016326:Extracellular Matrix Proteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C086539:BQ 788; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C072247:cyclo(Trp-Asp-Pro-Val-Leu)