Pathophysiology of atherosclerosis plaque progression

Area of Science:

• Cardiovascular Pathology
• Atherosclerosis Research
• Thrombosis Mechanisms

Background:

• Acute coronary syndromes (ACS) and sudden cardiac death are primarily caused by atherosclerotic plaque rupture leading to luminal thrombosis.
• The critical precursor lesion is the thin cap fibroatheroma (TCFA), also known as "vulnerable plaque".

Purpose of the Study:

• To elucidate the pathological progression of atherosclerotic lesions leading to plaque rupture and thrombosis.
• To detail the characteristics and contributing factors of different plaque morphologies causing thrombosis.

Main Methods:

• Review of pathological features of atherosclerotic plaques, including pathologic intimal thickening (PIT), fibroatheroma, and TCFA.
• Analysis of cellular and molecular mechanisms involved in plaque progression, necrotic core formation, and cap thinning.
• Identification of different thrombotic mechanisms: plaque rupture, plaque erosion, and calcified nodules.

Main Results:

• TCFA is characterized by a necrotic core and thin fibrous cap (≤65 μm), infiltrated by macrophages and T-lymphocytes.
• Intraplaque hemorrhage from vasa vasorum contributes to necrotic core expansion.
• Plaque erosion and calcified nodules represent less frequent but significant causes of thrombosis, particularly in specific demographics.

Conclusions:

• The progression from PIT to fibroatheroma involves macrophage infiltration and lipid pool conversion to a necrotic core.
• Macrophage-derived matrix metalloproteinases (MMPs) and smooth muscle cell apoptosis contribute to fibrous cap thinning, transforming fibroatheroma into TCFA.
• Understanding these distinct pathways is crucial for developing targeted therapies to prevent thrombotic cardiovascular events.