title: Computational modelling suggests good, bad and ugly roles of glycosaminoglycans in arterial wall mechanics and mechanobiology.
abstract: The medial layer of large arteries contains aggregates of the glycosaminoglycan hyaluronan and the proteoglycan versican. It is increasingly thought that these aggregates play important mechanical and mechanobiological roles despite constituting only a small fraction of the normal arterial wall. In this paper, we offer a new hypothesis that normal aggregates of hyaluronan and versican pressurize the intralamellar spaces, and thereby put into tension the radial elastic fibres that connect the smooth muscle cells to the elastic laminae, which would facilitate mechanosensing. This hypothesis is supported by novel computational simulations using two complementary models, a mechanistically based finite-element mixture model and a phenomenologically motivated continuum hyperelastic model. That is, the simulations suggest that normal aggregates of glycosaminoglycans/proteoglycans within the arterial media may play equally important roles in supporting (i.e. a structural role) and sensing (i.e. an instructional role) mechanical loads. Additional simulations suggest further, however, that abnormal increases in these aggregates, either distributed or localized, may over-pressurize the intralamellar units. We submit that these situations could lead to compromised mechanosensing, anoikis and/or reduced structural integrity, each of which represent fundamental aspects of arterial pathologies seen, for example, in hypertension, ageing and thoracic aortic aneurysms and dissections.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: S
authors.initials: S
authors.lastname: Roccabianca
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bellini
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT, USA jay.humphrey@yale.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Humphrey
mesh_terms: D000818:Animals; D002340:Carotid Artery Diseases / Q000473:pathology / Q000503:physiopathology*; D017536:Carotid Artery, Common / Q000473:pathology / Q000503:physiopathology*; D003198:Computer Simulation; D006025:Glycosaminoglycans / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D051379:Mice; D008955:Models, Cardiovascular; D011509:Proteoglycans / Q000378:metabolism*; D033081:Shear Strength; D013314:Stress, Mechanical; D013718:Tensile Strength; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology*
chemical_list: D006025:Glycosaminoglycans; D011509:Proteoglycans
keywords: anoikis; hyaluronan; mechanosensing; stress analysis; versican