Abstract Vulnerable plaque remains clinically undetectable, and there is no accepted in vitro model. We characterize the calcific nodules produced by calcifying vascular cells (CVC) in ApoE -null mice, demonstrating increased destabilization of cultured nodules in the presence of oxidized low-density lipoprotein (oxLDL) and monocytes under pulsatile shear stress. CVC implanted in the subcutaneous space of hyperlipidemic mice produced nodules revealing features of calcific atherosclerotic plaque including a fibrous cap, cholesterol clefts, thin shoulder, lipids, and calcium mineral deposits. CVC nodules seeded in the pulsatile flow channel ( τ avg = 23 dyn/cm 2 , ∂ τ/ ∂ t = 71 dyn·cm −2 ·s −1 ) underwent deformation and destabilization. Computational fluid dynamics revealed distinct shear force profiles on the nodules. Presence of oxLDL or monocytic THP-1 cells significantly increased the numbers of nodules destabilized from the substrate. Both oxLDL and THP-1 increased matrix metalloproteinase (MMP) activity in CVC. The MMP inhibitor GM6001 significantly reversed oxLDL- and THP-1-induced nodule destabilization, whereas overexpression of MMP-9 increased destabilization. These findings demonstrate that CVC-derived nodules resembled calcific atherosclerotic plaque and were destabilized in the presence of active lipids and monocytes via induction of MMPs. atherosclerosis plaque rupture calcifying vascular cells calcification Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print October 2011 , doi: 10.​1152/​ajpcell.​00313.​2011 Am J Physiol Cell Physiol February 2012 vol. 302 no. 4 C658-C665 » Abstract Free Full Text Free to you Full Text (PDF) Free to you Supplemental Videos All Versions of this Article: ajpcell.00313.2011v1 302/4/C658 most recent Classifications Vascular Biology Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Li, R. Articles by Hsiai, T. K. PubMed PubMed citation Articles by Li, R. Articles by Hsiai, T. K. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of Am J Physiol Cell Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

/lp/the-american-physiological-society/a-dynamic-model-of-calcific-nodule-destabilization-in-response-to-a3cd4mzfNA