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Macrophages play key roles in obesity-associated pathophysiology, including inflammation, atherosclerosis, and cancer, and processes that affect the survival-death balance of macrophages may have an important impact on obesity-related diseases. Adipocytes and other cells secrete a protein called extracellular nicotinamide phosphoribosyltransferase (eNampt;(More)
The endoplasmic reticulum (ER) unfolded protein response (UPR) restores equilibrium to the ER, but prolonged expression of the UPR effector CHOP (GADD153) is cytotoxic. We found that CHOP expression induced by ER stress was suppressed by prior engagement of toll-like receptor (TLR) 3 or 4 through a TRIF-dependent pathway. TLR engagement did not suppress(More)
Treatment of low density lipoprotein (LDL) with degrading enzymes transforms the molecule to a moiety that is micromorphologically indistinguishable from lipoproteinaceous particles that are present in atherosclerotic plaques, and enzymatically modified LDL (E-LDL), but not oxidized LDL (ox-LDL), spontaneously activates the alternative complement pathway,(More)
Combined treatment with trypsin, cholesterol esterase, and neuraminidase transforms LDL, but not HDL or VLDL, to particles with properties akin to those of lipid extracted from atherosclerotic lesions. Single or double enzyme modifications, or treatment with phospholipase C, or simple vortexing are ineffective. Triple enzyme treatment disrupts the ordered(More)
The mechanisms underlying the selective accumulation of macrophages in early atherosclerotic lesions are poorly understood but are likely to be related to specific properties of altered low density lipoprotein (LDL) deposited in the subendothelium. Enzymatic, nonoxidative degradation of LDL converts the lipoprotein to a potentially atherogenic moiety,(More)
OBJECTIVE to evaluate pedal bypass grafting in patients with diabetes mellitus with critical limb ischaemia. PATIENTS AND METHOD from 1994 to 1999, 49 consecutive pedal bypass grafts were performed in 46 patients with a median age of 69 years (range 37-85 years). The incidence of insulin-dependent diabetes mellitus was 87%. The distal anastomosis was(More)
The term ischemia-reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischemia with inadequate oxygen supply followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may both aggravate local injury as well as induce impairment of remote organ function. Conditions under(More)
PURPOSE To investigate the long-term outcome and efficacy of emergency treatment of acute aortic diseases with endovascular stent-grafts. METHODS From September 1995 to April 2007, 37 patients (21 men, 16 women; age 53.9 +/- 19.2 years, range 18-85 years) with acute complications of diseases of the descending thoracic aorta were treated by endovascular(More)
The human gut contains trillions of commensal bacteria, and similar to pathogenic bacteria, the gut microbes and their products can be recognized by toll-like receptors (TLRs). It is well acknowledged that the interaction between gut microbiota and the local TLRs help to maintain the homeostasis of intestinal immunity. High-fat intake or obesity can weaken(More)
It was the objective of this study to examine the role of human neutrophil granulocytes (PMN) in an in-vitro model of human neo-intima developed for the study of atherosclerosis. Human granulocytes were subjected to a co-culture model of human endothelial and smooth muscle cells. Subendothelial lipid accumulation was achieved by addition of native LDL to(More)