Myeloid HIF1α has only a minor impact on atherosclerosis development

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Atherosclerosis is an inflammatory disease driven by myeloid cells.
• Hypoxia in arterial walls is a key factor in atherosclerosis development.
• The role of hypoxia-inducible factors (HIFs) in myeloid cells during atherosclerosis is not fully understood.

Purpose of the Study:

• To investigate the role of myeloid-specific HIF-1α and HIF-2α in atherosclerosis.
• To determine the impact of HIFs on plaque formation and cardiac remodeling.

Main Methods:

• Generated myeloid-specific HIF-1α and HIF-2α knockout mice on an ApoE-/- background.
• Induced accelerated atherosclerosis using angiotensin II (AngII) infusion.
• Analyzed plaque formation, cardiac hypertrophy, and macrophage polarization.

Main Results:

• Myeloid HIF-1α, not HIF-2α, transiently limited cardiac hypertrophy in early AngII infusion.
• Aged mice with macrophage-specific HIF-1α knockout showed increased body weight and aortic plaque burden.
• HIF target gene expression was elevated in anti-inflammatory macrophage subsets in human atherosclerotic samples.

Conclusions:

• Myeloid HIF-1α plays a protective role in atherosclerosis, particularly in chronic hyperlipidemic conditions.
• Macrophage HIF-1α activity may promote reparative or stabilizing responses in atherosclerotic plaques.
• Targeting HIF-1α in myeloid cells could be a potential therapeutic strategy for atherosclerosis.