Abstract 17244: Monocytes and Oxidized Lipids Promote the Destabilization of Calcified Plaque Via Matrix Metalloproteinases(MMP)

• Published in: Circulation (New York, N.Y.) N.Y.), 2011-11, Vol.124 (suppl_21)
• Main Authors: Li, Rongsong, Mittelstein, David, Majumdar, Rohit, Lee, Juhyun, Tintut, Yin, Demer, Linda, Hsiai, Tzung
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.124.suppl_21.A17244

Abstract only Objective: Vascular calcification is closely associated with atherosclerosis, but whether it mechanically affects plaque stability remains controversial. We previously showed that calcific nodules produced with cultured calcifying vascular cells (CVC) were destabilized in response to shear stress. Here, we characterized the CVC-derived calcified nodules in ApoE-null mice, and assessed oxLDL and monocytes on the destabilization of CVC-derived calcified nodules under pulsatile shear stress (PSS). Methods and Results: To demonstrate that CVC-derived calcified nodules contain components of calcific atherosclerotic plaque in vivo, CVC was implanted in the ApoE-null mice via a cage. After 6 weeks, histology and immunohistochemsitry revealed a calcified plaque-like structure with fibrous caps, lipids, Collagen II, alkaline phosphotase and friable shoulders. To investigate the calcific nodule destabilization in vitro , CVC nodules were subjected to PSS for two and one-half hours. The percentage of nodules detached was calculated as quantification of nodule destabilization. Computational Fluid Dynamic (CFD) code simulated the instantaneous shear force distribution on the individual nodules and demonstrated accentuated instantaneous shear forces on the shoulder regions of nodules. Treatment with oxLDL or co-culture with monocytic THP-1 cells promoted the destabilization of nodules(Nodules detached: control (PSS) = 24±3%, PSS + THP-1=57±6%, PSS + oxLDL=45±7%, n=4, P