Grb2 is required for atherosclerotic lesion formation

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Immunology

Background:

• Grb2 is a linker protein activating mitogen-activated protein kinase (MAPK) cascades.
• MAPK activation is vital for macrophage proliferation and modified lipoprotein uptake in atherogenesis.
• The role of Grb2 in atherosclerosis pathogenesis is unclear.

Purpose of the Study:

• To investigate the role of the Grb2 adapter protein in atherosclerotic lesion formation.
• To generate and study Grb2 heterozygous (Grb2+/-) mice in an apolipoprotein E knockout (apoE-/-) background.

Main Methods:

• Generated Grb2+/- apoE-/- mice.
• Assessed atherosclerotic lesion formation using aortic sinus and en face assays.
• Performed bone marrow transplantation experiments.
• Conducted cell culture experiments with bone marrow-derived macrophages.

Main Results:

• Grb2+/- apoE-/- mice showed reduced atherosclerotic lesion formation on a Western diet compared to apoE-/- mice.
• Grb2 haploinsufficiency in blood-borne cells conferred resistance to atherosclerosis.
• Grb2 was essential for oxidized low-density lipoprotein (oxLDL)-induced MAPK activation and foam cell formation in macrophages.

Conclusions:

• Grb2 is required for atherosclerotic lesion development.
• Grb2 plays a critical role in the uptake of oxidized LDL by macrophages, a key process in atherosclerosis.