Scheda di revisione: Atherosclerosis Pathogenesis and Clinical Implications

1. 📌 Essentials

• Atherosclerosis is a chronic disease characterized by fatty deposits in arterial walls causing stenosis.
• Primarily affects medium to large arteries like coronary, carotid, and peripheral arteries.
• Initiates with endothelial dysfunction due to risk factors such as hypercholesterolemia, hypertension, smoking, and diabetes.
• Lipid infiltration, especially oxidized LDL, promotes inflammation and foam cell formation.
• Progressive stages include fatty streaks, fibrous plaques, and complicated lesions.
• Stable plaques are collagen-rich; unstable plaques are lipid-rich and prone to rupture.
• Critical stenosis >70–75% causes ischemic symptoms; rupture can lead to thrombosis.
• Clinical manifestations include angina, MI, stroke, limb ischemia, often asymptomatic early.
• Plaque development is a slow process spanning decades, beginning in youth.
• Morphological evolution: fatty streak → fibrous plaque → calcified and complex plaque.

2. 🧩 Key Structures & Components

• Endothelium — lines arteries, regulates vessel permeability and tone.
• Lipid core — composed of cholesterol, phospholipids, necrotic debris.
• Foam cells — macrophages engorged with oxidized LDL.
• Vascular smooth muscle cells (VSMCs) — migrate, proliferate, produce collagen.
• Fibrous cap — collagen layer stabilizing plaque.
• Necrotic core — lipid and cell debris prone to rupture.
• Calcifications — deposits within chronic plaques.
• Thrombus — clot formed after plaque rupture.
• Risk factors — hypercholesterolemia, hypertension, smoking, diabetes.
• Risk modifiers — age, sex, obesity, inactivity.

3. 🔬 Functions, Mechanisms & Relationships

• Endothelial dysfunction allows LDL to penetrate intima.
• Oxidized LDL induces monocyte adhesion and infiltration.
• Monocytes differentiate into macrophages, phagocytose lipids forming foam cells.
• Foam cells and lipid accumulation form fatty streaks.
• VSMCs migrate from media to intima, secrete collagen → fibrous cap.
• Stable plaques have thick collagen caps; unstable plaques have thin caps and large lipid cores.
• Plaque rupture exposes thrombogenic material, leading to thrombus formation.
• Critical stenosis (>70–75%) causes ischemic symptoms; rupture causes acute events.
• Calcification stabilizes plaques but can contribute to brittleness.

Endothelium
   │
   ├─ LDL infiltration
   │
   ▼
Oxidized LDL
   │
   ├─ Monocyte recruitment
   │
   ├─ Monocytes → macrophages → foam cells
   │
   ├─ Fatty streak formation
   │
   ├─ VSMC migration and collagen deposition
   │
   └─ Fibrous plaque
           │
           ├─ Stable (thick collagen)
           │
           └─ Unstable (lipid-rich core)

4. Comparative Table: Stable vs. Unstable Plaques

Feature	Stable Plaque	Unstable Plaque
Composition	Collagen-rich, dense cap	Lipid-rich, thin cap
Risk of rupture	Low	High
Presence of necrotic core	Small or absent	Large
Clinical risk	Chronic ischemia (angina)	Acute MI or stroke due to rupture
Morphology	Thick, fibrous	Thin, susceptible to fissure or rupture

5. 🗂️ Hierarchical Diagram

Atherosclerosis
 ├─ Initiation
 │   └─ Endothelial dysfunction
 ├─ Lipid infiltration
 │   └─ LDL cross-and oxidation
 ├─ Inflammatory response
 │   └─ Monocyte adhesion and infiltration
 ├─ Foam cell formation
 │   └─ Macrophages ingest oxidized LDL
 ├─ Plaque development
 │   ├─ Fatty streak
 │   ├─ Fibrous plaque (VSMC collagen)
 │   └─ Complex/ruptured plaque
 └─ Clinical outcome
     ├─ Chronic ischemia
     └─ Acute rupture leading to thrombus

6. ⚠️ High-Yield Pitfalls & Confusions

• Confusing fatty streaks with advanced plaques; fatty streaks are non-obstructive and benign.
• Mistaking stable plaques for unstable ones; stability depends on collagen content.
• Overlooking the role of oxidized LDL vs. native LDL.
• Ignoring the contribution of VSMCs to plaque stability.
• Misinterpreting the timing: initiation in youth (ages 10–20), symptoms often not until 35–40.
• Assuming all plaques cause symptoms; most early plaques are asymptomatic.
• Confusing atherosclerosis with arteriosclerosis (general arterial stiffening).
• Overemphasizing calcification as a sign of instability; often stabilizes plaques.

7. ✅ Final Exam Checklist

• Define atherosclerosis and identify affected arteries.
• List key risk factors: hypercholesterolemia, hypertension, smoking, diabetes.
• Describe the sequence: endothelial damage → LDL entry → foam cells → fatty streaks.
• Differentiate stable vs. unstable plaques.
• Know the critical stenosis percentage (>70–75%) causing symptoms.
• Understand the process of plaque rupture and thrombus formation.
• Recognize clinical presentations: angina, MI, stroke, gangrene.
• Recognize the significance of oxidized LDL in pathogenesis.
• Describe the morphological evolution of plaques.
• Recall age-related development starting at age 10–20.
• Be aware of factors that stabilize or destabilize plaques (collagen vs. lipids).
• Know the common arteries affected and related diseases.

End of Revision Sheet