Gelatinolytic Activity in Atherosclerotic Plaques Is Highly Localized and Is Associated With Both Macrophages and Smooth Muscle Cells In Vivo

Abstract

Background-Atherosclerosis is considered an inflammatory disease. Recent studies provided evidence for a predominant upstream location of plaque inflammation. The present study introduces a novel technique that evaluates the underlying mechanism of this spatial organization. Methods and Results-In hypercholesterolemic rabbits, atherosclerosis of the infrarenal aorta was induced by a combination of endothelial denudation and a high-cholesterol diet (2% cholesterol for 2 months). At the time of death, aortic vessel segments were dissected and reconstructed with a new technique that preserved the original intravascular ultrasound-derived lumen geometry. This enabled us to study the spatial relation of histological markers like macrophages, smooth muscle cells, lipids, gelatinolytic activity, and oxidized low-density lipoprotein. Results showed a predominant upstream localization of macrophages and gelatinase activity. Colocalization studies indicated that gelatinase activity was associated with macrophages and smooth muscle cells. Further analysis revealed that this was caused by subsets of smooth muscle cells and macrophages, which were associated with oxidized low-density lipoprotein accumulation. Conclusions-Upstream

Endothelial Cell–Specific FGD5 Involvement in Vascular Pruning Defines Neovessel Fate in Mice

“…Then, 5-m cryosections were double stained with Alexa Fluor-coupled isolectin IB4 (1:500; Invitrogen) and 1:100 mouse anti-FGD5 (Bioscience, Temse, Belgium), followed by FITC/rhodamin-labeled anti-mouse IgG antibody detection (1:500; Invitrogen, Breda, the Netherlands) and goat FAB against mouse IgG (HϩL) for blocking (Jackson Immunoresearch Laboratories, Sacramento, CA) as previously described. 18,19 …”

Ets2 Determines the Inflammatory State of Endothelial Cells in Advanced Atherosclerotic Lesions

“…Samples had been processed for immunohistological analysis, as well as protein extraction, and were quantified by two independent observers for histo-morphological indices of plaque vulnerability, as reported earlier 1 . CEA specimens are harvested, embedded in paraffin, and immunohistochemically examined for the presence of macrophages, VSMCs, collagen, endothelial cell (CD31+) and lipids.…”

“…A therosclerosis is a complex disease with a strong inflammatory component, [1][2][3][4] initially triggered by endothelial dysfunction and characterized by an influx of atherogenic lipoprotein components, combined with endothelial upregulation of proinflammatory cytokines and adhesion molecules. 5 Monocyte adhesion and extravasation perpetuate the disease by further differentiation into macrophages and foam cells, ultimately driving atherosclerotic lesion growth and complexity.…”

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

“…VSMC apoptosis is a critical factor for rupture-prone plaque formation. Clinical studies report that VSMCs mainly localize in the distal region of the vascular stenosis with low shear stress [128][129][130]. Increasing blood flow in vessel grafts induces endothelialization and inhibits neointimal hyperplasia [125,131], the molecular mechanism of which is based on the high expression of bone morphogenic proteins (BMP4) [132] and NO [123].…”