The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

Abstract

The formation of an atheroma begins when lipoproteins become trapped in the intima. Entrapped lipoproteins become oxidized and activate the innate immune system. This immunity represents the primary association between lipids and inflammation. When the trapping continues, the link between lipids and inflammation becomes chronic and detrimental, resulting in atherosclerosis. When entrapment ceases, the association between lipids and inflammation is temporary and healthy, and the atherogenic process halts. Therefore, the link between lipids and inflammation depends upon lipoprotein retention in the intima. The entrapment is due to electrostatic forces uniting apolipoprotein B to polysaccharide chains on intimal proteoglycans. The genetic transformation of contractile smooth muscle cells in the media into migratory secretory smooth muscle cells produces the intimal proteoglycans. The protein, platelet-derived growth factor produced by activated platelets, is the primary stimulus for this genetic change. Oxidative stress is the main stimulus to activate platelets. Therefore, minimizing oxidative stress would significantly reduce the retention of lipoproteins. Less entrapment decreases the association between lipids and inflammation. More importantly, it would halt atherogenesis. This review will analyze oxidative stress as the critical link between lipids, inflammation, and the pathogenesis of atherosclerosis. Through this perspective, we will discuss stopping oxidative stress to disrupt a harmful association between lipids and inflammation. Numerous therapeutic options will be discussed to mitigate oxidative stress. This paper will add a new meaning to the Morse code distress signal SOS-stopping oxidative stress.

Keywords: lipoprotein retention; oxidative stress; platelet-derived growth factor; proteoglycans; remnant cholesterol; smooth muscle cell transformation.

Figure 1

Comprehensive schematic of the role oxidative stress plays in cardiovascular disease. The multiplicity of risk factors for cardiovascular disease that drive oxidative stress which in turn results in a well-defined cascade of events that drive the development of atheroma in the vessel is presented. These cellular events lead to a decrease in lifespan and an increase in dementia and cancer risk. The linkage between lipids and inflammation is a critical consideration in the management of cardiovascular disease. Reduction in critical risk factors and the judicious use of medications (blue) can reduce levels of oxidative stress and in turn halt the progression of events leading to the development of atheroma.