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

Kazunobu Ishikawa1, Mohamad Navab, Aldons J Lusis

  • 1The First Department of Internal Medicine and Center for Medical Education and Career Development, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1625, Japan.

Insights

Heme oxygenase-1 (HO-1) deficiency in mice causes severe arterial inflammation and lipid peroxidation. HO-1 plays a crucial role in preventing cardiovascular disease by suppressing inflammation and oxidative stress.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Biochemistry

Background:

  • Heme oxygenase-1 (HO-1) is an enzyme with known cytoprotective functions.
  • Its specific roles in the cardiovascular system, particularly in chronic inflammation and lipid metabolism, require further elucidation.

Purpose of the Study:

  • To investigate the function of HO-1 in the cardiovascular system.
  • To analyze the impact of HO-1 deficiency on arterial inflammation and lipid profiles in aged mice.

Main Methods:

  • Analysis of one-year-old homozygous HO-1-knockout mice and wild-type littermates.
  • Assessment of cardiovascular pathology, including aortitis and coronary arteritis.
  • Measurement of plasma lipid levels (total cholesterol, HDL, triglyceride), HDL composition (apolipoprotein ratio), paraoxonase activity, and lipid hydroperoxides.

Main Results:

  • HO-1-knockout mice exhibited severe aortitis and coronary arteritis with mononuclear cell infiltration and fatty streaks.
  • Despite similar total cholesterol and HDL levels, knockout mice showed lower body weight and plasma triglyceride.
  • HO-1 deficiency led to a significant alteration in HDL composition, a 10-fold reduction in apolipoprotein AI to AII ratio, decreased paraoxonase activity, and elevated plasma lipid hydroperoxides.

Conclusions:

  • HO-1 deficiency promotes severe systemic arterial inflammation and atherosclerosis development, even on a standard diet.
  • HO-1 plays a critical protective role against oxidative stress and lipid peroxidation in the cardiovascular system.
  • These findings highlight HO-1 as a potential therapeutic target for cardiovascular diseases characterized by inflammation and oxidative damage.

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