Expression of genes related to oxidative/nitrosative stress in mouse hearts: effect of preconditioning and cholesterol diet.

Abstract

BACKGROUND:

The aim of our study was to explore the effect of high-cholesterol diet and preconditioning on cardiac gene expression patterns in mouse hearts, focusing on genes involved in nitric oxide (NO) and free radical signaling and the mevalonate pathway.

MATERIAL/METHODS:

Mice were fed 2% high-cholesterol or normal diet for 8 weeks. Hearts isolated from both groups were subjected to either a preconditioning (PC) protocol (3 cycles of 5 min ischemia and 5 min aerobic perfusion) or a time-matched non-preconditioning protocol followed by 30 min global test ischemia and 2 hour reperfusion.

RESULTS:

PC altered gene expression only in the mice subjected to a normal diet, as shown in neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS) and the superoxide-producing enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4. The rate-limiting enzyme of the mevalonate pathway, 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase showed differential expression in the myocardium in response to I/R and PC in mice on normal diet but not in cholesterol-fed animals.

CONCLUSIONS:

We conclude that cholesterol-enriched diet leads to alterations in preconditioning-induced gene expression in the mouse heart, which might lead to marked changes of oxidative/nitrosative stress signaling and to the attenuation of the cardioprotective effect of preconditioning.

• Authors: Gabriella F Kocsis, Tamas Csont, Zoltan Varga-Orvos, Laszlo G Puskas, Zsolt Murlasits, Peter Ferdinandy
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 16 Issue 1 Pg. BR32-9 (Jan 2010) ISSN: 1643-3750 [Electronic] United States
• PMID: 20037483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, Dietary
• DNA Primers
• Nitric Oxide Synthase
• Xanthine Oxidase
• NADH, NADPH Oxidoreductases
• NADPH Oxidase 1
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, mouse
• Mevalonic Acid

Topics

• Analysis of Variance
• Animals
• Cholesterol, Dietary (toxicity)
• DNA Primers (genetics)
• Gene Expression Regulation (drug effects, physiology)
• Heart (physiology)
• Hypercholesterolemia (metabolism)
• Ischemic Preconditioning, Myocardial
• Male
• Mevalonic Acid (metabolism)
• Mice
• Myocardium (metabolism)
• NADH, NADPH Oxidoreductases (metabolism)
• NADPH Oxidase 1
• NADPH Oxidase 4
• NADPH Oxidases (metabolism)
• Nitric Oxide Synthase (metabolism)
• Oxidative Stress (physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Xanthine Oxidase (metabolism)