Atherosclerosis Development and Progression: The Role of Atherogenic Small, Dense LDL

Jelena Vekic,Alper Sonmez,Arrigo F G Cicero,Andrej Janez,Manfredi Rizzo,Anca Pantea Stoian,Aleksandra Zeljkovic

doi:10.3390/medicina58020299

Abstract

Atherosclerosis is responsible for large cardiovascular mortality in many countries globally. It has been shown over the last decades that the reduction of atherosclerotic progression is a critical factor for preventing future cardiovascular events. Low-density lipoproteins (LDL) have been successfully targeted, and their reduction is one of the key preventing measures in patients with atherosclerotic disease. LDL particles are pivotal for the formation and progression of atherosclerotic plaques; yet, they are quite heterogeneous, and smaller, denser LDL species are the most atherogenic. These particles have greater arterial entry and retention, higher susceptibility to oxidation, as well as reduced affinity for the LDL receptor. Increased proportion of small, dense LDL particles is an integral part of the atherogenic lipoprotein phenotype, the most common form of dyslipidemia associated with insulin resistance. Recent data suggest that both genetic and epigenetic factors might induce expression of this specific lipid pattern. In addition, a typical finding of increased small, dense LDL particles was confirmed in different categories of patients with elevated cardiovascular risk. Small, dense LDL is an independent risk factor for cardiovascular diseases, which emphasizes the clinical importance of both the quality and the quantity of LDL. An effective management of atherosclerotic disease should take into account the presence of small, dense LDL in order to prevent cardiovascular complications.

Highlights

The disorders of lipoprotein metabolism are considered as important factors for the initiation and progression of atherosclerosis, and analysis of standard lipid status parameters is a mandatory step in cardiovascular disease (CVD) risk assessment, prevention and therapeutic management
We have demonstrated that the relation between proprotein convertase subtilisin/kexin type 9 (PCSK9) and sdLDL particles in type 1 diabetes mellitus (DM) youths is modulated by the extent of achieved glycemic control [47]
We have shown that Low-density lipoproteins (LDL) particle size decreases gradually during pregnancy and that increased presence of sdLDLs is associated with smaller weight, length and head circumference of newborns [69]

Summary

Introduction

The disorders of lipoprotein metabolism are considered as important factors for the initiation and progression of atherosclerosis, and analysis of standard lipid status parameters is a mandatory step in cardiovascular disease (CVD) risk assessment, prevention and therapeutic management. A residual cardiovascular risk, attributable to sdLDL, still might persist even if the patient achieves its LDL-C target value [8] These data suggests that a finding of increased sdLDL could guide the treatment individualization in specific groups of patients with metabolic disorders. Dense LDL particles are integral part of the lipid triad or atherogenic lipoprotein phenotype (ALP), which includes elevated TG and reduced high density lipoproteins (HDL) levels [13]. This characteristic lipid pattern is a common feature of dyslipidemia in patients with metabolic syndrome and type 2 diabetes mellitus (DM) [14,15]

HDL sdLDL

Conclusions