Diseases that enhance LDL oxidation include diabetes and hypertriglyceridemia (115). Hyperglycemia increases LDL oxidation, in part, through an increase in glycation products, which subsequently enhances free radical production in stimulated inflammatory cells (115). Insulin and IGF-I cause an upregulation of LDL receptor and down regulation of HDL receptor (281). Insulin increases uptake and esterification of
LDL-C by VSMC (3). LDL from diabetic patients is more atherogenic and more likely to be bound (by affinity chromatography on Ricinus communis agglutinin-agarose). Bound LDL has lower sialic acid content and higher fructosyl lysine level, and induces cholesterol accumulation in cultured cells and has lower neutral lipids. Desialylated LDL has a low neutral carbohydrate level, decreased content of major lipids, small size, high density, increased electronegative charge, less phospholipids, and unesterified cholesterol on their surface, with resultant altered tertiary Apo B structure with more exposure of proteoglycans-binding regions and high affinity binding of small dense LDL to arterial proteoglycans. Secretary phospholipase A2 (PLA2) in arterial tissue or plasma reduces phospholipid content in the surface monolayer LDL leading to the formation of small, dense LDL with an enhanced tendency to interact with proteoglycans. The circulating level of secretary phospholipase A2-IIA is an independent risk factor for CAD. Transgenic mice expressing human group IIA secretory phospholipid A2 spontaneously develop atherosclerotic lesions with lower HDL-C and higher LDL/VLDL-C. Also, group IIAs PLA2 can contribute to atherosclerotic lesion development through a mechanism independent of systemic lipoprotein metabolism (402) However, in mice, endogenous mouse secretory phospholipase All gene does not significantly affect HDL or atherosclerosis (403\ reviewed in ref. 404). Incubation of LDL with serum induces desialylation, through enzymes close to sialyltransferase, leading to the above changes in addition to loss of a-tocopherol from LDL, increased LDL susceptibility to oxidation, and accumulation of cholesterol covalently bound to Apo B, a marker of lipoperoxidation. Therefore, in diabetics LDL is smaller, denser, electronegative, desialylated, and glycated (405^407; and reviewed in ref. 408). However, a different study concluded that asialylated LDL has little value as a risk factor for coronary atherosclerosis in CAD patients (409). Large numbers of small Apo B 100-containing lipoproteins are far more atherogenic than lower numbers of large Apo B 100-containing lipoproteins despite nearly identical cholesterol levels (reviewed in ref. 410). Thus, both hyperinsulinemia and increased oxidation of LDL-C likely contribute to the accelerated atherosclerosis of diabetes mellitus.
The role of Apo B containing lipoproteins other than LDL has been reviewed in ref. 411. (3VLDL enhances iNOS expression and nitrite accumulation in IL-1 |3-stimulated VSMC (412). In rat aortic SMC, remnant lipoproteins transactivate EGF receptor via PKC and the shedding of membrane-bound soluble heparin-binding EGF-like growth factor from SMCs, resulting in SMC proliferation (413).
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All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.