Abstract 18925: Enhanced Cellular Proliferation and Altered Collagen Deposition May Accelerate Atherosclerosis in Human Peripheral Artery Disease: Implication of Morphological Predictors in Restenotic Plaque Progression
Introduction: The mechanisms responsible for restenosis include cellular and extracellular matrix (ECM) overproduction mediated by vascular smooth muscle cell (SMC) migration and proliferation. However, the role of the myofibroblast is less clear.
Hypothesis: This study was designed to evaluate the role of the myofibroblast in ECM overproduction mediated by stellate cell proliferation and reparative collage III deposition in restenotic tissue from patients with symptomatic peripheral arterial disease.
Methods: Fourteen de novo and seventeen restenotic superficial femoral artery plaques were obtained in-vivo and compared for cell proliferation, SMC (α-actin), fibroblast specific protein-1 (FSP1), and vimentin by immunochemistry, type I and type III collagens by Picro-sirius red stain and polarization microscopy. Stellate cell morphology was graded by scoring. Cellular co-localization of α-actin with vimentin, FSP-1, percentage of apoptosis (active caspase 3) and percentage of cell proliferation (Ki67) were done by confocal microscopy.
Results: See figure and table. In restenotic atheroma, increased proliferation of myofibroblasts and SMCs were associated with higher content of reparative type III collagen (p= 0.0001) compared to de novo plaques. Furthermore, percent proliferative index of actin with Ki67 and percent apoptosis of actin were increased in restenotic plaques (p= 0.0001).
Conclusions: In peripheral artery disease restenosis, increased myofibroblasts, and proliferative SMC may preferentially enhance atheroma progression and may predispose to increased type III collagen deposition. This may contribute for the severity of clinical manifestation seen in PAD. The molecular pathways associated with these differences including apoptosis are under active investigation.
Author Disclosures: P. Krishnan: None. P. K-Raman: None. M. Purushothaman: None. J.C. Kovacic: None. A. Tarricone: None. M. Vasquez: None. W. Jose: None. A. Kini: None. S.K. Sharma: None. V. Fuster: None. P.R. Moreno: None.
- © 2014 by American Heart Association, Inc.