HIF-1alpha overexpression and experimental murine atherosclerosis

Area of Science:

• Immunology
• Cardiovascular Biology
• Molecular Biology

Background:

• Lymphocytes are crucial in atherosclerosis pathogenesis.
• Hypoxia-inducible factor-1 (HIF-1) modulates T cell activation and cytokine production, impacting inflammation.
• The role of HIF-1alpha in lymphocytes concerning atherosclerosis requires further investigation.

Purpose of the Study:

• To investigate the effects of HIF-1alpha overexpression in lymphocytes on experimental atherosclerosis in ApoE knockout mice.
• To determine if modulating HIF-1alpha influences T helper cell responses and inflammatory markers.

Main Methods:

• ApoE-/- mice received hydrodynamic injection of a mutated, stabilized HIF-1alpha construct or an empty plasmid.
• HIF-1alpha expression in spleen cells was confirmed.
• Splenocyte cytokine profiles (IL-10, IFN-gamma) were analyzed using RT-PCR.
• T helper cell polarization was assessed via antibody array.
• Aortic sinus lesion size and IFN-gamma expression in lymphocytes and aortas were evaluated.

Main Results:

• HIF-1alpha overexpression was successfully achieved in recipient mouse spleen cells.
• Increased IL-10 and decreased IFN-gamma expression were observed in splenocytes from HIF-1alpha-treated mice.
• A shift from T helper 1 to T helper 2 immune response was detected.
• HIF-1alpha injection led to a significant reduction in aortic plaque size.
• Reduced IFN-gamma expression was noted in CD4+ lymphocytes and aortas.

Conclusions:

• HIF-1alpha expression in lymphocytes attenuates experimental atherosclerosis.
• Reduced IFN-gamma expression is a key mechanism linking HIF-1alpha to atherosclerosis improvement.
• Modulating HIF-1alpha in lymphocytes presents a potential therapeutic strategy for atherosclerosis.