Acute coronary syndrome (ACS) occurs when a plaque in the coronary arteries ruptures or erodes, restricting blood flow. Plaque forms over time as LDL cholesterol builds up in artery walls due to risk factors like smoking, diabetes, and hypertension. The plaque contains an inflammatory necrotic core covered by a fibrous cap. Rupture occurs when the cap thins, exposing the core and triggering a clot. Medications treat ACS by lowering cholesterol and inflammation to stabilize plaques and prevent clots.

1. Acute coronary
syndrome
part 1
By: Arwa

2. Introduction
• Acute coronary syndrome (ACS) is the most common
disease caused by plaque formation in coronary
arteries where it can lead to:
• Occlusion: no blood supply to the heart
• Rupture: bleeding
• Or congestion: slow blood flow
• My goal is to get a clear explanation on how plaque
lead to ACS and how each medication works to treat
such condition.

3. Risk factors
• When the patient…
• Has high concentration of lipid in his blood specially LDL
• Diabetic
• Smoker
• Hypertensive
• Male
• He will have high risk of getting atherosclerosis
• Atherscleosis is the aerly stages of plaque formation where
arterial walls thickens as a result of fat accumolation

4. Atherosclerotic plaque
formation

5. main reference of this
educational material

6. Site of injury
• what makes atherosclerosis to occur in more specific
areas than others?
• Low endothelial shear stress
• Meaning the frictional force(parallel) that blood flow exerts on
vessel wall
• Location: near branch points and inner curvatures
• Coronary arteries are one of the most affected arteries.

7. Shear stress
• When the blood flow inside the artery the friction
between the endothelium and blood components
• It increase with small arterial radius (narrow arteries)
• Decrease by viscous blood (red/white blood cells
,platelets and body temperature) meaning when the
blood become thin the friction lessens
• in normal state shear stress
• promotes vasodilation and anti-thrombogenicity
• suppress growth and pro-inflammatory factors

8. Did you know..?
• That blood considered as non-Newtonian fluid meaning
its viscosity change whether it flows slowly or fast
despite the (e.g. Water) that remains unaffected by flow
rate

9. Mechanisms
• Lipoprotein retention
• Inflammatory cells
recruitment
• Foam cell formation
• Apoptosis and necrosis
• Smooth muscle cells
proliferation
• Angiogenesis
• Fibrosis
• Calcification
• Arterial remodeling
• Fibrous cab rupture
• Thrombosis

10. Lesion development sequence

11. LDL
accumulation
Chronic
stimulation of
immune
system
Macrophages
(M) &
dendritic
cells (D)
Immune cells
lead to lesion
development
LDL+M+D=foam
cells
Foam cells
+foam cells=
Xanthoma

12. What is next
accumulation of
acellular lipid
rich material in
the intima
• Without disruption of intimal
structure (pathological intimal
thickening)
Macrophages
invasion and
apoptosis
• Lipid core grows into
necrotic core
Impaired
removal of
apoptotic
remnant
• Undergo 2ry necrosis
Necrotic core
form
(fibroatheroma)
• Further
inflammation

13. Angiogenesis
• Neovessels originate from
vasa vasorum of adventitia
• To provide alternative
pathway of monocytes
• These vessels are fragile
and leaky causing plasma
protein and erythrocyte to
leak leading intraplaque
bleeding
• Which will expand necrotic
core and increase
inflammation

14. Fibrosis
• In intimal layer structural changes occurs in the smooth
muscle cells
Contractile phenotype
SMC’S
• Small cells
• Decreased ECM
production
• Increased contractile
protein expression
• Decreased migration
Synthetic phenotype SMC’S
• Large cells
• Increased ECM production
• Decreased contractile
protein expression
• Increased migration

16. How does synthetic SMC’s occur
• Proliferation of medial SMC’S
• Migration (which undergo phenotypic modulation) from
media into intima

17. Calcification
• When artery calcifies it
indicates for progressed
atherosclerosis
• Apoptotic cells,
extracellular matrix and
necrotic core all act as a
(nest) for calcium
granules which
accumulate leading to
calcium deposit
formation

18. Arterial remodeling
• It is one way of the body to maintain balance
between tissue demand and blood supply
• The arterial remodeling occurs as response to
progressed plaque development it is not well
understood what provokes such mechanism

19. • The positive remodeling can regress to become
negative remodeling as an effect of drug therapy (anti-
hyperlipidemic agents)
Positive remodeling Negative remodeling
Macrophages accumulation
Hemorrhage
Larger lipid core
Thinner fibrous cab
Fibrotic
Vulnerable to rupture Stable plaque
Most of ACS case CCS
Caused by hypercholesterolemia Caused by DM, HTN, smoking

20. Articles helps understanding
remodeling

21. Diagnosis

22. General equation
• To measure the ratio of remodeling
• EEM area at lesion site/EEM area at reference site
• EEM (external elastic membrane)
• If the result <0.95 (negative)
• If the result >1.05 (positive)

23. The negative remodeling the lumenal area starts narrowing inward
**Notice the difference between EEM in the images below and
lumen narrowing**

24. In contrast, The positive remodeling shows extremely expanding
plaque with slightly narrowed luminal area

25. Plaque rupture
• Usually the rupture occur at the cap thinnest region
(<65 μm in thickness)
• What makes the fibrous cap to thin ?
• Gradual loss of smooth muscle cells
• Macrophages infiltration that secretes :
• Plasminogen activator
• Cathepsins
• Matrix Metalloproteinase (ECM degradation)

26. A & B : The white area in the lumen represent the necrotic core NC
and the fibrous cap FC which is extremely thin (high risk)
C & D: shows that area near the fibrous cab has abundant!
macrophages and the other parts are not inflamed

27. Then what is plaque erosion
• It is superficial disruption of fibromuscular plaque without a
core
• Where plaque rupture is a disruption of fibrous cap over a
lipid core
• It is characterized by :
• Absent/disrupted endothelium
• Great proliferation of SMC’s
• Less presence of macrophages
• Abundant proteoglycans
• Thrombus formed because of disrupted intima
• Common leading cause to STEMI and sudden cardiac
death

28. Ruptured plaque has inflammatory cells and much lipid with thinner
fibrous cab than the eroded plaque which has more smooth muscle cells
and proteoglyans and less lipid but absent endothelium
Inflammatory cells

29. Thrombosis
• Factors affecting thrombotic response(Virchow's triad):
• Thrombogenicity of exposed plaque material
(Thrombogenic lipid core & cap collagen)
• Local flow disturbances (microemboli may be washed
away leading to distal embolization of the myocardium)
• Systemic response propensity(e.g. smoking)

30. Thrombosis
 Two types of thrombus can form:
White thrombus Red thrombus
Platelet rich thrombus RBC rich thrombus
Forms in high ESS areas Low ESS areas
Cause partial clotting Total occlusion
Cause UN/NSTEMI STEMI