Plaque erosion risk and JAK2 V617F variant

Area of Science:

• Cardiovascular Medicine
• Hematology
• Genetics

Background:

• Clonal haematopoiesis of indeterminate potential (CHIP) is linked to increased myocardial infarction (MI) risk.
• The JAK2 V617F mutation within CHIP substantially elevates MI risk.
• The specific mechanisms linking JAK2 V617F to MI subtypes, plaque erosion and rupture, are not well understood.

Purpose of the Study:

• To investigate the association between JAK2 V617F mutations and the mechanisms of myocardial infarction (MI), specifically plaque erosion and plaque rupture.
• To explore the potential role of neutrophil activation in the link between JAK2 V617F and MI erosion.

Main Methods:

• Case-control studies involving 728 erosion cases, 919 rupture cases, and 804 controls.
• Digital-drop polymerase chain reaction (PCR) used to detect JAK2 V617F.
• Single-cell RNA sequencing performed on neutrophils from JAK2 V617F carriers and healthy donors.

Main Results:

• JAK2 V617F carriers (VAF ≥1%) were significantly more prevalent in erosion patients (3.57%) compared to rupture patients (.76%) and controls (.37%).
• Logistic regression showed a strong association between JAK2 V617F and erosion (OR 16.246, P < .0001), but not rupture (OR 1.677, P = .495).
• Neutrophils from JAK2 V617F carriers exhibited heightened expression of genes related to activation, adhesion, migration, and granule secretion.

Conclusions:

• JAK2 V617F is significantly associated with an increased risk of myocardial infarction due to plaque erosion.
• Enhanced neutrophil activation in JAK2 V617F carriers may be a key mechanism contributing to plaque erosion and subsequent MI.