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Hypercholesterolemia Abrogates Late Preconditioning Via A Tetrahydrobiopterin-dependent Mechanism In Conscious Rabbits.

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Hypercholesterolemia Abrogates Late Preconditioning Via A Tetrahydrobiopterin-dependent Mechanism In Conscious Rabbits.

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Hypercholesterolemia abrogates late preconditioning via a tetrahydrobiopterin-dependent mechanism in conscious

Xian-Liang Tang¹, Hitoshi Takano, Yu-Ting Xuan

¹Institute of Molecular Cardiology, University of Louisville, The Jewish Hospital Heart and Lung Institute, Louisville, KY, USA.

|September 28, 2005

View abstract on PubMed

Summary

This summary is machine-generated.

Hypercholesterolemia blocks the heart-protective effects of late ischemic preconditioning (PC) by inhibiting tetrahydrobiopterin (BH4) upregulation. This mechanism is crucial for maintaining cardioprotection in the absence of high cholesterol.

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Area of Science:

Cardiovascular Physiology
Molecular Cardiology
Ischemic Heart Disease

Background:

Late ischemic preconditioning (PC) offers cardioprotection in healthy models.
The effect of hypercholesterolemia on late PC remains unclear.
Tetrahydrobiopterin (BH4) is a critical cofactor in cardiovascular function.

Purpose of the Study:

To investigate if hypercholesterolemia affects the infarct-sparing effect of late PC.
To determine if BH4-dependent pathways mediate the loss of late PC in hypercholesterolemia.

Main Methods:

Conscious rabbits with normal or high cholesterol diets were subjected to ischemic PC.
Coronary occlusion and reperfusion protocols were used to induce myocardial infarction.
BH4 levels and the effect of a BH4 synthesis inhibitor (N-acetylserotonin) were assessed.

Main Results:

In normocholesterolemic rabbits, PC reduced infarct size and increased myocardial BH4.
In hypercholesterolemic rabbits, PC failed to reduce infarct size or increase BH4.
Inhibition of BH4 synthesis abolished the protective effects of PC in normocholesterolemic rabbits.

Conclusions:

Hypercholesterolemia abrogates the infarct-sparing effect of late PC and blunts BH4 upregulation.
BH4 synthesis inhibition mimics the effect of hypercholesterolemia on late PC.
Hypercholesterolemia impairs late PC by preventing BH4 upregulation, essential for inducible nitric oxide synthase.