**Author details**

402 Lipoproteins – Role in Health and Diseases

proliferation and oxidative stress.

reduced antioxidant properties.

**6. Concluding remarks** 

individuals.

oxidation.

undergo dehydration reactions and rearrange themselves to finally form AGE, which are responsible for many of the irreversible pathological effects seen in diabetes. The receptors for AGE (RAGE) are abundantly expressed on vascular endothelial cells, smooth muscle cells and macrophages, which are enhanced in atherosclerotic lesions in diabetes. Since Ox-LDL has AGE epitopes, it binds RAGE on macrophages and enhances macrophage

Like oxidation, glycation of LDL prevents LDLr-mediated cellular uptake of lipoproteins and promotes scavenger receptor-mediated uptake. *In vivo*, small, dense, which is more atherogenic than large buoyant LDL, appears to be preferentially glycated; also, *in vitro* studies suggest that it is more susceptible to glycation (Soran & Durrington, 2011). Diabetic individuals display higher plasma concentrations of glycated LDL than non-diabetic

Type 1 diabetes subjects have lipid disorders (diabetic dyslipidemia), with a pro-atherogenic lipid profile: increased concentration of TG and LDL cholesterol, low HDL levels (Verges, 2009). In addition, they display increased cholesterol-triglyceride ratio within their VLDL, increased triglyceride in their LDL and HDL, glycation of apolipoproteins, increased oxidation of LDL and an increase in small dense LDL (relatively more atherogenic). HDL from Type 1 diabetes subjects is less effective in promoting cholesterol efflux and has

Subjects with Type 2 diabetes also have a proatherogenic lipid profile with quantitative and qualitative differences in their lipoproteins (Verges, 2005). Typically, they have increased triglyceride levels, increased VLDL production and decreased VLDL catabolism, and decreased HDL cholesterol levels. They have large VLDL particles that are richer in triglyceride, small dense LDL particles, increase in triglyceride content of LDL and HDL, Ox- and glycated-LDL, glycation of apolipoproteins and increased susceptibility of LDL to

In conclusion, this chapter has provided a broad overview of the role of oxidative stress, ROS, and lipoprotein oxidation in the pathophysiology of disease states such as atherosclerosis, Alzheimer's disease and diabetes. While Ox-LDL and inflammation seem to be bona fide factors in the development of atherosclerosis, the role of dysfunctional HDL in these disease states is not known at this point. There are several points of uncertainty regarding the *in vivo* source of ROS and oxidative stress, the physiological behavior of oxidized lipoproteins, particularly in Alzheimer's disease and diabetes, and the line-up of antioxidants and autoantibodies in response to the oxidized factors. It is anticipated that the next decade will provide more insights into the molecular and mechanistic basis of the effect of oxidative damage on lipoprotein in disease states. This would pave the way for new

therapeutic options for preventing and treating these diseases.

Vikram Jairam *Yale University School of Medicine, USA* 

Koji Uchida *Nagoya University, Japan* 

Vasanthy Narayanaswami *California State University Long Beach, USA* 
