Triggers of plaque rupture may occur spontaneously

Triggers of Plaque Rupture
•
May occur spontaneously
•
Other factors that may serve as triggers:
↑ blood pressure

↑ shear force
↑ force of cardiac contraction
↑ coronary blood flow
•
Plaque rupture  collagen exposure 
platelet aggregation & coagulation
cascade activation  thrombus formation

Photo adopted from:
101/F1
Vulnerable
Plaque
Plaque
Rupture
Thrombus
ACS

Thrombus Formation
•
Fibrin & platelets form a clot on top of the ruptured plaque
•
#1) Platelets aggregate and form a platelet plug
–
Adhesion to disrupted endothelium
–
Activation

Release mediators (ADP, TXA
2
, thrombin) → Activates surrounding
platelets
–
Aggregation

Platelet activation leads to conformational change of glycoprotein IIb/IIIa
(GPIIb/IIIa) surface receptors of platelets
–
Fibrinogen binds to GPIIb/IIIa receptors → Links platelets together →
Aggregation
•
Tissue factor in ruptured plaque activates extrinsic
coagulation pathway
–
Formation of thrombin → fibrin

Platelet Aggregation
Photo adopted from:
von Willebrand factor (vWF) is a cell adhesion ligand, which under normal conditions, helps endothelial cells adhere to collagen
in the basement membrane. When the BV is injured, collagen, vWF, and tissue factor from the subendothelium are exposed to
the bloodstream. When platelets contact exposed collagen or wWf, they are activated causing platelet aggregation.

Platelet Aggregation
Photo adopted from:
Platelet activators  ADP: Adenosine diphosphate, TXA2: Thromboxane A2

White vs. Red Clot
•
White clot
–
Contains more platelets than fibrin

Platelets give the clot a “white” color

Typically occurs in NSTE ACS
–
Usually produces incomplete occlusion of coronary lumen
•
Red clot
–
Contains more fibrin and red blood cells than platelets

Fibrin stabilize clots and trap red blood cells giving it a “red”
appearance

Typically occurs in STE MI
–
Usually produces complete occlusion of coronary lumen

Acute coronary syndrome
Stable angina

Pathogenesis of ACS
Atherosclerotic plaque with
a lipid-rich core and thin
fibrous cap
Plaque rupture
Thrombus formation over
lesion
Acute coronary syndrome
Shear forces, inflammation,
apoptosis
Platelet adhesion,
activation, and
aggregation; production of
thrombin
Acute ↓ in coronary blood
flow

Myocardial Infarction
•
“Heart attack”
•
Results from persistent ischemia (not quickly
reversed) or from complete occlusion of a
coronary artery
•
Effect on myocardium
–
Necrotic (nonviable)
–
Often dysfunctional

Often leads to heart failure
Photo adopted from:

Myocardial Ischemia
• Inadequate supply of O
2
to meet myocardial O
2
demand (MVO
2
)



O
O
2
demand in face of fixed supply causes ischemia
demand in face of fixed supply causes ischemia


PAIN!