George Kuriakose

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Excess cellular cholesterol induces apoptosis in macrophages, an event likely to promote progression of atherosclerosis. The cellular mechanism of cholesterol-induced apoptosis is unknown but had previously been thought to involve the plasma membrane. Here we report that the unfolded protein response (UPR) in the endoplasmic reticulum is activated in(More)
Macrophages in advanced atherosclerotic lesions accumulate large amounts of unesterified, or "free," cholesterol (FC). FC accumulation induces macrophage apoptosis, which likely contributes to plaque destabilization. Apoptosis is triggered by the enrichment of the endoplasmic reticulum (ER) with FC, resulting in depletion of ER calcium stores, and induction(More)
ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stress-induced apoptosis may affect advanced atherosclerosis. Here we placed Apoe-/- mice deficient in macrophage p38alpha MAPK on a Western diet and found that they(More)
Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J(More)
We provide analytical models for capacity evaluation of an infrastructure IEEE 802.11 based network carrying TCP controlled file downloads or full-duplex packet telephone calls. In each case the analytical models utilize the attempt probabilities from a well known fixed-point based saturation analysis. For TCP controlled file downloads, following Bruno et(More)
Microsomal triglyceride transfer protein (MTP) is needed to assemble chylomicrons in the endoplasmic reticulum (ER) of enterocytes. We explored the role of an ER stress protein, inositol-requiring enzyme 1beta (IRE1beta), in regulating this process. High-cholesterol and high-fat diets decreased intestinal IRE1beta mRNA in wild-type mice. Ire1b(-/-) mice fed(More)
OBJECTIVE Atherosclerotic plaques that are prone to disruption and acute thrombotic vascular events are characterized by large necrotic cores. Necrotic cores result from the combination of macrophage apoptosis and defective phagocytic clearance (efferocytosis) of these apoptotic cells. We previously showed that macrophages with tyrosine kinase-defective(More)
OBJECTIVE Macrophage apoptosis plays important roles in atherosclerosis. Bcl-2 is a key cell survival molecule, but its role in macrophage apoptosis in atherosclerosis is not known. The goal herein was to determine the effect of macrophage-targeted deletion of Bcl-2 on macrophage apoptosis in atherosclerotic lesions of Apoe(-/-) mice. METHODS AND RESULTS(More)
Macrophage death in advanced atherosclerotic lesions leads to lesional necrosis and likely promotes plaque instability, a precursor of acute vascular events. Macrophages in advanced lesions accumulate large amounts of unesterified cholesterol, which is a potent inducer of macrophage apoptosis. We have shown recently that induction of apoptosis in cultured(More)
OBJECTIVE The key initial step in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Acid sphingomyelinase (acid SMase), an enzyme present extracellularly within the arterial wall, strongly enhances lipoprotein retention in model systems in vitro, and retained lipoproteins in human plaques are enriched in ceramide, a(More)