Carotid Atherosclerosis Progression and ACAT Inhibition—Reply
- Raphaël Duivenvoorden, MD r.duivenvoorden@amc.uva.nl;
- Eric de Groot, MD, PhD;
- John J. P. Kastelein, MD, PhDAcademic Medical CenterAmsterdam, the Netherlands
Since this article does not have an abstract, we have provided the first 150 words of the full text.
- KEYWORDS:
- ACAT1 PROTEIN, HUMAN
- ACYLTRANSFERASES
- ATHEROSCLEROSIS
- CAROTID ARTERY DISEASES
- CHOLESTEROL, LDL
- DISEASE PROGRESSION
- DRUG THERAPY
- EZETIMIBE
- HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS
- HYPERLIPIDEMIAS
- PACTIMIBE
- STEROL O-ACYLTRANSFERASE
In Reply: Dr Parini and colleagues are critical that our article did not provide evidence that pactimibe inhibits ACAT-1 and ACAT-2. However, we could not specifically address this issue because the CAPTIVATE study was not designed for this purpose. Studies to assess enzyme specificity and pharmacodynamics are typically performed in earlier drug-development phases.
Parini et al suggest that we should have discussed the potential harmful effects of ACAT-1 inhibition. We did discuss that ACAT-1 inhibition might lead to accumulation of free cholesterol in macrophages, an effect that could lead to cell death. These properties suggest that ACAT-1 inhibitors are not beneficial as an antiatherosclerotic drug.
Parini et al also express their doubt that ACAT-2 might be up-regulated in human lesions, while they claim that evidence that ACAT-2 is functional in human lesions is lacking. We disagree; ACAT-2, in addition to ACAT-1, has been found to be expressed in fully differentiated …
