The class
One week of a high-cholesterol diet paradoxically shrinks myocardial infarct size in CETP-transgenic mice (Coron Artery Dis 2001)
Original title: Acute exposure to a high cholesterol diet attenuates myocardial ischemia-reperfusion injury in cholesteryl ester transfer protein mice
To define CETP's role in myocardial infarction after acute cholesterol exposure, researchers fed CETP-transgenic mice a normal chow diet, a high-cholesterol diet for one week, or a high-cholesterol diet for six weeks, then subjected them to 30 minutes of coronary occlusion and 2 hours of reperfusion. Infarct size (percentage of area at risk) was significantly smaller after one week of the high-cholesterol diet (18.7 plus or minus 7.0%) than after the normal diet (51.4 plus or minus 5.5%) or six weeks of the high-cholesterol diet (44.4 plus or minus 5.2%, P less than 0.05), accompanied by less neutrophil infiltration and a significantly lower reduced-to-oxidized glutathione ratio (1.5 plus or minus 0.1, P less than 0.01) in the one-week group, showing brief acute cholesterol exposure attenuates ischemia-reperfusion injury in this CETP-transgenic model.
Original abstract
Background: Previous experiments have demonstrated that acute exposure to a high-cholesterol diet (HCD) increases the severity of myocardial infarction in animals. Recent results suggest that the process is modulated by multiple genes and their interactions with circulating cholesterol.
Design: In the present study cholesteryl-ester-transfer-protein (CETP) transgenic mice were generated and fed a normal rodent-chow diet, HCD for 1 week, or a HCD for 6 weeks in order to define the role of CETP in myocardial infarction after acute exposure to a HCD.
Methods: Cholesterol levels in mice of all groups were measured. Separate groups of mice were exposed to 30 min of in-vivo occlusion of coronary artery and 2 h of reperfusion. We assessed the sizes of the ischemic zone and infarct using Evans blue and 2,3,5-triphenyltetrazolium chloride.
Results: The extent of infarction (percentage infarct/area at risk) was significantly less (P < 0.05) after 1 week of a HCD (18.7 +/- 7.0%) than those for the normal diet group (51.4 +/- 5.5%) and the group fed a HCD for 6 weeks (44.4 +/- 5.2%). Additionally, there was significantly less infiltration of neutrophils into the ischemic-reperfused mouse hearts for mice fed a HCD for 1 week. Levels of reduced and oxidized glutathione in the hearts of CETP mice were measured for separate groups of animals. The reduced:oxidized-glutathione ratio was significantly (P < 0.01) lower for mice fed a HCD for 1 week (1.5 +/- 0.1) than it was for mice fed a normal diet (3.6 +/- 0.3) and a HCD for 6 weeks (3.3 +/- 0.2).
Conclusions: These data suggest that activity of CETP in hypercholesterolemic mice has an acute effect on size of infarct after 1 week of a HCD. This suggests that CETP induces tolerance of ischemia in the mice fed a HCD via mild oxidative stress.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.