Regression of atherosclerosis: which components regress and what influences their reversal

Area of Science:

• Cardiovascular Medicine
• Pathology
• Biochemistry

Background:

• Atherosclerosis presents with two distinct features: atherosis, characterized by lipid infiltration, and sclerosis, involving connective tissue deposition and endothelial dysfunction.
• Endothelial dysfunction impairs endothelium-derived relaxing factor (EDRF) release, leading to reduced arterial compliance.

Purpose of the Study:

• To investigate the differential impact of lipid lowering on the atherosis and sclerosis phases of atherosclerosis.
• To explore therapeutic strategies for established fibrous plaques in advanced atherosclerosis.

Main Methods:

• Review of clinical trial evidence regarding lipid-lowering therapies (e.g., LDL-C reduction) in various stages of atherosclerosis.
• Analysis of functional and structural changes in arterial compliance and plaque composition.

Main Results:

• Atherosis, characterized by lipid infiltration, is generally reversible with low-density lipoprotein cholesterol (LDL-C) reduction.
• While maximal LDL-C lowering can improve arterial compliance in established fibrous plaques (sclerosis), structural abnormalities persist.
• Regression of established fibrous plaques is slow in native arteries and absent in bypass grafts with maximal LDL-C reduction.

Conclusions:

• Lipid lowering is most effective in the early atherosis phase of atherosclerosis.
• Advanced atherosclerosis with significant connective tissue sclerosis may require therapeutic agents beyond lipid lowering for plaque reversal.
• Functional improvements in sclerosis can be achieved through maximal LDL-C reduction, likely via EDRF normalization, despite persistent structural changes.