title: Biophysical induction of vascular smooth muscle cell podosomes.
abstract: Vascular smooth muscle cell (VSMC) migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP) secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu), however little is known about the physiological cues that drive podosome formation. We present the first evidence that physiological, physical stimuli mimicking cues present within the microenvironment of diseased arteries can induce podosome formation in VSMCs. Both microtopographical cues and imposed pressure mimicking stage II hypertension induce podosome formation in A7R5 rat aortic smooth muscle cells. Moreover, wounding using a scratch assay induces podosomes at the leading edge of VSMCs. Notably the effect of each of these biophysical stimuli on podosome stimulation can be inhibited using a Src inhibitor. Together, these data indicate that physical cues can induce podosome formation in VSMCs.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Kohn
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Huynh
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Carey
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Brooke N
authors.initials: BN
authors.lastname: Mason
authors.affiliation: Divison of Vascular Surgery at Mount Sinai Hospital, New York, New York, United States of America.
authors.forename: Ageliki G
authors.initials: AG
authors.lastname: Vouyouka
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Reinhart-King
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D055592:Biophysical Phenomena / Q000502:physiology; D002460:Cell Line; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D000069261:Podosomes / Q000502:physiology*; D051381:Rats; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D019061:src-Family Kinases