Small, Dense Low-Density Lipoprotein-Cholesterol and Atherosclerosis: Relationship and Therapeutic Strategies

Abstract

Low-density lipoprotein cholesterol (LDL-C) plays an important role in the formation, incidence, and development of atherosclerosis (AS). Low-density lipoproteins can be divided into two categories: large and light LDL-C and small, dense low-density lipoprotein cholesterol (sdLDL-C). In recent years, an increasing number of studies have shown that sdLDL-C has a strong ability to cause AS because of its unique characteristics, such as having small-sized particles and low density. Therefore, this has become the focus of further research. However, the specific mechanisms regarding the involvement of sdLDL-C in AS have not been fully explained. This paper reviews the possible mechanisms of sdLDL-C in AS by reviewing relevant literature in recent years. It was found that sdLDL-C can increase the atherogenic effect by regulating the activity of gene networks, monocytes, and enzymes. This article also reviews the research progress on the effects of sdLDL-C on endothelial function, lipid metabolism, and inflammation; it also discusses its intervention effect. Diet, exercise, and other non-drug interventions can improve sdLDL-C levels. Further, drug interventions such as statins, fibrates, ezetimibe, and niacin have also been found to improve sdLDL-C levels.

Sorting through the extensive and confusing roles of sortilin in metabolic disease

“…In recent years, an increasing number of studies demonstrating that small dense LDLs have a greater propensity to cause atherosclerosis have emerged. This has propelled researchers to further investigate the mechanism behind the atherogenicity of small dense LDLs in order to develop new therapies to prevent cardiovascular events and to establish a clinically effective method to accurately measure circulating small dense LDL levels ( 240 , 241 , 242 , 243 ).…”

Diabetic dyslipidemia impairs coronary collateral formation: An update

“…T2DM is usually accompanied by oxidation or glycation of LDL, and glycoxidatively modified LDL poses more pro-atherogenic and antiangiogenic properties than native LDL ( 27 ). In addition, the predominance of sdLDL-C confers a threefold increased risk for CAD, owning to their greater propensity for endothelial penetration into arterial wall, lower binding affinity for LDL receptor, longer circulation time, and higher susceptibility to glycation, oxidative modification, and uptake by scavenger receptors ( 28 ). The prospective Framingham offspring study and large cohort studies suggest that sdLDL is superior to LDL-C and other biomarkers in predicting future cardiovascular events in stable CAD patients with T2DM or hypertriglyceridemia ( 29 – 31 ).…”

Modulation of Lipid Profile and Lipoprotein Subfractions in Overweight/Obese Women at Risk of Cardiovascular Diseases through the Consumption of Apple/Berry Juice

“…Recently, studies support that sdLDL is a good CVD risk biomarker [ 54 , 55 , 56 ] and is strongly associated with atherosclerotic risk markers, such as inflammation, thrombosis, hematological markers, and prediabetes [ 55 , 56 ]. To identify and quantify atherogenic (LDL3-7) and non-atherogenic sdLDL subfractions (LDL1 and LDL2) in plasma, a polyacrylamide gel electrophoresis (Lipoprint system) was used.…”