Acute exposure to a high cholesterol diet attenuates myocardial ischemia-reperfusion injury in cholesteryl ester transfer protein mice.

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.

• Authors: S P Jones, W G Girod, K R Marotti, T Y Aw, D J Lefer
• Journal: Coronary artery disease (Coron Artery Dis) Vol. 12 Issue 1 Pg. 37-44 (Feb 2001) ISSN: 0954-6928 [Print] England
• PMID: 11211164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Cholesterol Ester Transfer Proteins
• Cholesterol, Dietary
• Glycoproteins

Topics

• Animals
• Carrier Proteins (physiology)
• Cholesterol Ester Transfer Proteins
• Cholesterol, Dietary (administration & dosage)
• Glycoproteins (physiology)
• Hemodynamics
• Hypercholesterolemia (physiopathology)
• Male
• Mice
• Mice, Transgenic
• Myocardial Infarction (physiopathology)
• Myocardial Reperfusion Injury (physiopathology)