Understanding intraplaque hemorrhage: From pathogenesis to clinical impact in atherosclerosis

Area of Science:

• Cardiovascular Pathology
• Atherosclerosis Research
• Vascular Biology

Background:

• Atherosclerotic cardiovascular disease is a leading global cause of death.
• Intraplaque hemorrhage (IPH) is increasingly recognized as a driver of plaque progression.
• IPH actively promotes plaque destabilization, not just passive volume expansion.

Purpose of the Study:

• To elucidate the molecular and cellular mechanisms by which intraplaque hemorrhage (IPH) drives atherosclerotic plaque destabilization.
• To highlight the role of IPH as a central biological driver of plaque progression and vulnerability.
• To explore the translational potential of in vivo imaging for detecting IPH and its clinical implications.

Main Methods:

• Review of accumulating pathological evidence on intraplaque hemorrhage (IPH).
• Analysis of molecular and cellular responses within hemorrhagic plaques, including erythrocyte lysis and macrophage activation.
• Examination of advances in vascular imaging for in vivo detection of IPH-related plaque features.

Main Results:

• Erythrocyte lysis in IPH generates oxidative stress and accelerates necrotic core expansion.
• Hemoglobin-haptoglobin uptake by macrophages induces a phenotype promoting angiogenesis and inflammation.
• IPH-driven processes amplify endothelial dysfunction, impair fibrous-cap integrity, and suppress calcification, increasing rupture susceptibility.
• In vivo imaging of IPH correlates with accelerated lesion progression and adverse cardiovascular outcomes.

Conclusions:

• Intraplaque hemorrhage (IPH) is a critical, active driver of atherosclerotic plaque progression and destabilization.
• IPH initiates interconnected pathways that amplify plaque vulnerability.
• Understanding IPH mechanisms may reveal novel therapeutic targets and improve identification of high-risk patients.