Vascular Smooth Muscle Cells in Atherosclerosis

Area of Science:

• Cardiovascular Biology
• Cellular Biology
• Pathology

Background:

• Historically, vascular smooth muscle cells (VSMCs) were thought to be homogenous and primarily involved in plaque formation and stabilization.
• This view is challenged by recent genetic studies revealing VSMC phenotypic switching into less-differentiated, macrophage-like cells.
• This switching directly contributes to atherosclerosis development.

Purpose of the Study:

• To review the complex role of VSMCs in atherosclerosis, moving beyond the traditional view.
• To explore the impact of VSMC phenotypic switching, embryological origin, and cellular processes on plaque development and stability.
• To highlight the critical need for a comprehensive understanding of VSMC behavior for therapeutic advancements.

Main Methods:

• Review of genetic lineage tracing studies.
• Analysis of evidence regarding VSMC origins and behavior.
• Examination of VSMC phenotypic switching, proliferation, apoptosis, and senescence in atherogenesis.

Main Results:

• VSMC phenotypic switching leads to less-differentiated cells, including macrophage-like cells, which promote atherosclerosis.
• VSMC proliferation may be beneficial throughout atherogenesis, not just in advanced lesions.
• VSMC apoptosis, senescence, and derived macrophage-like cells can exacerbate inflammation.

Conclusions:

• The traditional view of VSMCs in atherosclerosis is outdated; phenotypic switching is a key driver.
• Understanding the diverse behaviors and origins of VSMCs is essential for targeting atherosclerosis.
• Comprehensive knowledge of VSMC dynamics offers critical therapeutic targets for prevention and treatment.