Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Science

Background:

• Atherosclerosis is a leading cause of death, particularly in individuals with diabetes, obesity, and insulin resistance.
• The role of Akt2 (a serine-threonine protein kinase) in atherosclerosis progression is currently unknown.

Purpose of the Study:

• To investigate the specific contribution of Akt2 to the development and progression of atherosclerosis.
• To elucidate the mechanisms by which Akt2 influences macrophage function in the context of atherosclerosis.

Main Methods:

• Utilized germ-line Akt2-deficient mice and Ldlr(-/-) mice for atherosclerosis studies.
• Employed bone marrow transplantation to assess the role of Akt2 in hematopoietic cells.
• Conducted in vitro studies on macrophages to evaluate migration, cholesterol metabolism, and inflammatory responses.

Main Results:

• Germ-line Akt2 deficiency did not alter atherosclerotic plaque size despite higher lipids and glucose.
• Transplantation of Akt2-deficient bone marrow significantly reduced atherosclerosis progression in Ldlr(-/-) mice.
• Akt2 deficiency impaired macrophage migration, reduced cholesterol accumulation, and promoted an M2-like phenotype in response to inflammatory stimuli.

Conclusions:

• Macrophage Akt2 plays a critical role in regulating macrophage migration, inflammatory responses, and cholesterol metabolism during atherosclerosis.
• Targeting Akt2 specifically within macrophages presents a potential therapeutic strategy for treating atherosclerosis.