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.

Oxidative Stress Underpins Clinical, Social, and Genetic Risk Factors for Atherosclerotic Cardiovascular Disease

“… 9 Without OS, most lipoproteins transcytose through endothelial cells without getting trapped or oxidized. 10 However, endothelial inflammation results from a host of insults on the arterial endothelial lining via OS. The imbalance of prooxidant and antioxidant forces, resulting in OS, causes endothelial permeability, and oxidizes low-density lipoproteins (oxLDL).…”

“… 9 The OxLDL readily enters the subendothelial space (due to increased endothelial permeability), gets trapped, and aggregates, which are critical steps in atheroslcerosis. 10 …”

“…PDGF promotes the transformation of contractile smooth muscle cells (SMCs) to migratory secretory SMCs, which migrate to the deep layer of the endothelial intima. 10 ROS can also promote this transformation. 9 Migratory secretory SMCs produce “sticky” proteoglycans, which trap the oxLDL in the arterial intima.…”

“… 9 Migratory secretory SMCs produce “sticky” proteoglycans, which trap the oxLDL in the arterial intima. 10 , 12 SMCs also produce cytokines, further worsening inflammation. 13 …”

“… 10 All of these processes perpetuate inflammation, therefore sustaining the OS. 3 , 10 The immune-mediated monocytes differentiate into macrophages, which phagocytize the oxLDL and become engorged. 10 , 14 This process creates pathognomonic foam cells, the hallmark of the early atherosclerotic fatty streak.…”