High-density Lipoprotein and Low-density Lipoprotein Therapeutic Approaches in Acute Coronary Syndromes

Abstract

Background: Low-density lipoprotein cholesterol (LDL), and especially its oxidized form, renders the atherosclerotic plaque vulnerable to rupture in acute coronary syndromes (ACS). On the other hand, high-density lipoprotein (HDL) is considered an anti-atherogenic molecule. The more recent HDL-targeted drugs may prove to be superior to those used before. Indeed, delipidated HDL and HDL mimetics are efficient in increasing HDL levels, while the apoA-I upregulation with RVX-208 appears to offer a clinical benefit which is beyond the HDL related effects. HDL treatment however has not shown a significant improvement in the outcomes of patients with ACS so far, studies have therefore focused again on LDL. In addition to statins and ezetimibe, novel drugs such as PSCK9 inhibitors and apolipoprotein B inhibitors appear to be both effective and safe for patients with hyperlipidemia.

Conclusion: Data suggest these could potentially improve the cardiovascular outcomes of patient with ACS. Yet, there is still research to be done, in order to confirm whether ACS patients would benefit from LDL- or HDL-targeted therapies or a combination of both.

Keywords: High-density lipoprotein; acute coronary syndromes; atherosclerosis; ezetimibe; lipidlowering drugs; low-density lipoprotein; outcomes; statins.

Fig. (1)

The atherogenic role of LDL vs. the atheroprotective properties of HDL. The deposition of the oxidized LDL in the intima media is the first crucial step that leads to the formation of a nascent atheroma. Oxidized LDL particles promote the inflammatory process, as they enhance the expression of adhesion molecules. Monocytes accumulate into the vessel wall, where they mature into tissue macrophages and subsequently into lipid-laden foam cells. These processes cause endothelial dysfunction and exacerbate the thrombotic status. By contrast, HDL mitigates the atherosclerotic process as it presents anti-inflammatory, anti-oxidative and anti-thrombotic properties, which enhance endothelial integrity. HDL also promotes cholesterol efflux from the artery wall and prevents the increase of the necrotic core volume. LDL: low-density lipoprotein; HDL: high-density lipoprotein; ox-LDL: oxidized LDL; NO: nitric oxide; PGI2: prostacyclin; SMCs: smooth muscle cells; RBCs: red blood cells.

Fig. (2)

Differences in HDL and LDL structure. Lipoprotein particles consist of two basic components: an internal core – an aggregate of cholesteryl esters and triglycerides – and an external phospholipid monolayer, which contains apolipoproteins and unesterified cholesterol. The different lipoproteins are discriminated based on the quantity and specific class of apoliporoteins they contain. 50% of an HDL particle is made up of protein, while the equivalent percentage for an LDL particle is 25%. Apo A-I and apo A-II make up 90% of the HDL’s protein mass, while each LDL particle contains a single apo-B-100 molecule. HDL: high density lipoprotein; LDL: low-density lipoprotein; apo A-I: apolipoprotein A-I.