Apolipoprotein E-/- Mice Lacking Hemopexin Develop Increased Atherosclerosis via Mechanisms That Include Oxidative...

Area of Science:

• Cardiovascular Biology
• Immunology
• Metabolic Diseases

Background:

• Hemopexin (Hx) is a heme scavenger that increases under atherogenic conditions.
• Hx is known to mitigate oxidative damage with macrophages.
• The specific role of Hx in atherosclerosis development remained unclear.

Purpose of the Study:

• To investigate the role of hemopexin (Hx) in the development of atherosclerosis.
• To determine if Hx influences oxidative stress, lipoprotein inflammation, and macrophage function in atherosclerosis.

Main Methods:

• Utilized Hx and apoE double-knockout (HxE(-/-)) mice for atherosclerosis studies.
• Compared HxE(-/-) mice with control apoE(-/-) mice, analyzing circulating factors and aortic pathology.
• Assessed macrophage polarization, cholesterol efflux, and the effects of Hx administration in vivo and ex vivo.

Main Results:

• HxE(-/-) mice exhibited elevated free heme, reactive oxygen species, and proinflammatory HDL.
• Significantly increased atherosclerotic plaque area and macrophage infiltration were observed in HxE(-/-) mice.
• Hx administration reduced heme levels, and ex vivo Hx pretreatment shifted macrophages towards an M2-like phenotype.

Conclusions:

• Hemopexin (Hx) plays a novel protective role in atherosclerosis.
• Hx alleviates heme-induced oxidative stress and improves HDL inflammatory properties.
• Hx modulates macrophage phenotype and function, inhibiting atherosclerosis progression in apoE(-/-) mice.