Atherothrombosis and high-risk plaque: part I: evolving concepts

Area of Science:

• Cardiovascular pathology
• Immunology
• Biochemistry

Background:

• Atherothrombosis involves cholesterol deposition, inflammation, and thrombus formation, leading to plaque rupture or erosion.
• Current American Heart Association (AHA) classification lacks criteria for thin cap fibroatheroma and plaque erosion, common causes of vulnerable plaques.
• The disease progresses through five phases, from early lesions to plaque rupture, healing, and fibrocalcification.

Purpose of the Study:

• To review emerging classifications for atherothrombosis, addressing limitations of the current AHA system.
• To analyze the multifaceted roles of cholesterol, inflammation, and immune responses in atherothrombosis progression.
• To systematically evaluate mechanisms of plaque rupture and thrombosis in advanced atherothrombosis.

Main Methods:

• Review of existing literature and emerging classifications for atherothrombosis.
• Analysis of histological criteria and their limitations in current systems.
• Systematic evaluation of cellular and molecular mechanisms in early and advanced atherothrombosis phases.

Main Results:

• The AHA classification is insufficient for high-risk plaques like thin cap fibroatheroma and plaque erosion.
• Endothelial dysfunction, cholesterol transport, lipoproteins, proteoglycans, immune responses, and calcification are key in early phases.
• Eccentric remodeling, vasa vasorum neovascularization, plaque rupture mechanisms, and tissue factor in thrombosis are critical in advanced stages.

Conclusions:

• New classifications are needed to accurately categorize atherothrombosis, particularly high-risk plaques.
• Understanding the progression from early lesions to plaque rupture and thrombosis is crucial for managing acute coronary events.
• The link between inflammation, plaque rupture, and thrombogenicity highlights the complexity of atherothrombosis.