Update on the role of acyl-CoA: Cholesterol acyltransferase inhibitors in atherosclerosis

R. Doshi, J. Wu, R. Fishelevich, A. Rodriguez

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Cardiovascular disease is one of the leading causes of mortality and morbidity in industrialised nations. Hypercholesterolaemia is one of a number of risk factors identified that influences the development and progression of atherosclerosis. While drugs such as HMGCoA reductase inhibitors or statins have been shown to significantly reduce cholesterol levels and the risk for cardiovascular disease, there is still a pressing need to identify other compounds that might further reduce the risk. One such class of drugs, currently in preclinical and clinical studies, is acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors. Two isoforms of ACAT have been identified; ACAT1 has a more ubiquitous distribution in steroidogenic tissue, pancreas, intestine and macrophages and ACAT2 is predominantly expressed in hepatocytes and intestines. In human tissues, ACAT2 expression is high in foetal hepatocytes but declines in adult hepatocytes. Its expression remains unchanged in foetal and adult human intestines. ACAT enzymes participate in the assembly of chylomicrons and very low density lipoproteins (triglyceride rich lipoprotein) and also in the formation of cholesteryl ester storage droplets within cells residing in the vessel wall. The initial results from preclinical and clinical studies suggest that ACAT inhibitors may have a beneficial effect in altering lipid profiles and in retarding the progression of atherosclerotic disease.

Original languageEnglish (US)
Pages (from-to)1655-1662
Number of pages8
JournalExpert Opinion on Therapeutic Patents
Issue number11
StatePublished - 2001


  • Acyl-CoA:cholesterol acyltransferase (ACAT)
  • Atherosclerosis
  • Foam cells
  • Hypercholesterolaemia
  • Hyperlipidaemia
  • Hypertriglyceridaemia

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


Dive into the research topics of 'Update on the role of acyl-CoA: Cholesterol acyltransferase inhibitors in atherosclerosis'. Together they form a unique fingerprint.

Cite this