Regression of atherosclerosis: lessons learned from genetically modified mouse models.

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Translational Medicine

Background:

• Atherosclerosis regression is a critical clinical goal.
• Advancements in murine models have facilitated research into regression mechanisms.
• Understanding regression is vital for developing targeted therapies.

Purpose of the Study:

• To review recent mouse studies on atherosclerosis regression.
• To highlight molecular mechanisms underlying plaque regression.
• To discuss therapeutics targeting atherosclerosis regression.

Main Methods:

• Utilized consistent murine models for atherosclerosis regression research.
• Included aortic transplant models.
• Employed Reversa mouse models, gene complementation, and dietary interventions.

Main Results:

• Atherosclerosis regression involves distinct molecular processes, not simply reversed progression.
• Key features include macrophage depletion (reduced recruitment, increased egress, decreased proliferation).
• Plaque macrophages shift to an anti-inflammatory phenotype, necrotic cores shrink, and fibrous caps organize. Type 1 diabetes impedes regression; some interventions show promise.

Conclusions:

• Mouse models have significantly advanced the understanding of atherosclerosis regression mechanisms.
• These insights are crucial for identifying novel therapeutic targets for lesion resolution.