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


METHODS
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.
Jones
S P
SP
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130, USA.
Girod
W G
WG
Marotti
K R
KR
Aw
T Y
TY
Lefer
D J
DJ
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006023:Glycoproteins / Q000502:physiology*; D006439:Hemodynamics; D006937:Hypercholesterolemia / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*
D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D006023:Glycoproteins