Vasculitis, Atherosclerosis, and Altered HDL Composition in Heme-Oxygenase-1-Knockout Mice

Abstract EN

To elucidate roles of heme oxygenase-1 (HO-1) in cardiovascular system, we have analyzed one-year-old HO-1-knockout mice.

Homozygous HO-1-knockout mice had severe aortitis and coronary arteritis with mononuclear cellular infiltration and fatty streak formation even on a standard chow diet.

Levels of plasma total cholesterol and HDL were similar among the three genotypes.

However, homozygous HO-1-knockout mice had lower body weight and plasma triglyceride.

HO-1-deficiency resulted in alteration of the composition of HDL.

The ratio of apolipoprotein AI to AII in HO-1-knockout mice was reduced about 10-fold as compared to wild-type mice.

In addition, paraoxonase, an enzyme against oxidative stress, was reduced less than 50% in HO-1-knockout mice.

The knockout mice also exhibited significant elevation of plasma lipid hydroperoxides.

This study using aged HO-1-knockout mice strengthened the idea that HO-1 functions to suppress systemic inflammation in artery wall and prevents plasma lipid peroxidation.