title: Amyloid Beta Influences Vascular Smooth Muscle Contractility and Mechanoadaptation.
abstract: Amyloid beta accumulation in neuronal and cerebrovascular tissue is a key precursor to development of Alzheimer's disease and can result in neurodegeneration. While its persistence in Alzheimer's cases is well-studied, amyloid beta's direct effect on vascular function is unclear. Here, we measured the effect of amyloid beta treatment on vascular smooth muscle cell functional contractility and modeled the mechanoadaptive growth and remodeling response to these functional perturbations. We found that the amyloid beta 1-42 isoform induced a reduction in vascular smooth muscle cell mechanical output and reduced response to vasocontractile cues. These data were used to develop a thin-walled constrained mixture arterial model that suggests vessel growth, and remodeling in response to amyloid betamediated alteration of smooth muscle function leads to decreased ability of cerebrovascular vessels to vasodilate. These findings provide a possible explanation for the vascular injury and malfunction often associated with the development of neurodegeneration in Alzheimer's disease.
authors: Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 554555 e-mail: haldx002@umn.edu.
authors: Eric S
authors: ES
authors: Hald
authors: Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 554555 e-mail: timmx182@umn.edu.
authors: Connor D
authors: CD
authors: Timm
authors: Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 554555 e-mail: pwalford@umn.edu.
authors: Patrick W
authors: PW
authors: Alford
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008955:Models, Cardiovascular; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D014469:Umbilical Arteries / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C000605559:amyloid beta-protein (11-42)