REVIEW

Prospects for atherosclerosis regression through increase in high-density lipoprotein and other emerging therapeutic targets

Justin M S Lee, Robin P Choudhury

Department of Cardiovascular Medicine, University of Oxford, Oxford, UK

Correspondence to:
R P Choudhury
Department of Cardiovascular Medicine, Level 5 John Radcliffe Hospital, Oxford OX3 9DU, UK; robin.choudhury{at}cardiov.ox.ac.uk

In a process often seen as progressive and irreversible, deposition and retention of lipoproteins and the consequent inflammatory reaction result in the accumulation of atherosclerotic plaques from an early age. However, striking effects observed in experimental models support the concept that atherosclerosis can regress. This is often accompanied by changes in plaque composition favouring stability and decreased likelihood of rupture. Large clinical trials have established the value of low-density lipoprotein cholesterol reduction with statin treatment, although this may prevent no more than 30% of all cardiovascular events, and the magnitude of effect on plaque regression seems relatively modest. High-density lipoprotein cholesterol (HDL-C) is well recognised as an important and independent protective factor, although treatment options to increase HDL-C have until now been limited. The recent emergence of new treatments will probably establish increased HDL-C as another important strategy in antiatherosclerosis treatment. Beyond HDL-C increases, further appreciation of mechanisms of cellular lipid homoeostasis and regulation of gene transcription have revealed new targets for atherosclerosis treatment. This review considers emerging approaches to plaque regression together with some of the parallel developments in imaging technology that will improve our appreciation of response to treatment.

Abbreviations: ACAT, acyl-coenzyme A:cholesterol acyltransferase; apo, apolipoprotein; ApoAIMilano, a mutant form of apoAI; BIP, bezafibrate infarction prevention; CETP, cholesteryl ester transfer protein; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; LXR, liver X receptor; PPAR, peroxisome proliferator-activated receptor

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