Risk Factors for Atherosclerosis:

A. Major Factors:

Non-modifiable:
1. Increasing age
2. Male gender
3. Family history
4. Genetic abnormalities

Modifiable:
1. Hyperlipidemia (specially Familial hypercholesterolemia)
2. Hypertension
3. Diabetes
4. Smoking cigarettes
5. CRP (C-Reactive Protein)

B. Minor Factors:
1. Obesity
2. Physical inactivity
3. Stress (Type A personality)
4. Postmenopausal estrogen deficiency
5. High carbohydrate intake
6. Altered lipoprotein(a)
7. Transunsaturated fat intake
8. Chlamydia infection

Pathogenesis:

Atherosclerosis as defined by response to injury hypothesis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium.
1. Chronic endothelial injury mediated by various factors like hyperlipidemia, hypertension, smoking, toxins, immune reactions, hemodynamic factors, etc.

2. With chronic hyperlipidemia (low HDL and high LDL, abnormal lipoprotein), lipoproteins accumulate within the intima.

3. Endothelial dysfunction (increased permeability, leukocyte adhesion)

4. Endothelial cells express: VCAM-1 binds monocyte and T lymphocyte.
After monocytes adhere to the endothelium, they:
(a) migrate between Endothelial cells to localize in the intima
(b) transform into macrophages and engulf lipoproteins (largely oxidized LDL) to from foam cells

5. Macrophages produce
(a) IL-1 and TNF, which increase adhesion of leukocytes.
(b) Reactive oxygen species : cause oxidation of the LDL
(c) Growth factors that may contribute to Smooth muscle cell proliferation.

6. The activated leukocytes and intrinsic arterial cells can release fibrogenic mediators

7. Smooth muscle cell response:
Smooth Muscel Cells migrate from the media to the intima and proliferate and deposit ECM to form fibrofatty atheroma
Growth factors: PDGF, FGF, and TGF-α
Smooth Muscle Cells may also take up modified lipids, contributing to foam cell formation.

Complications:

1. Stenosis
2. Rupture
3. Ulceration
4. Erosion
5. Atheroemboli
6. Hemorrhage
7. Thrombosis
8. Aneurysm

Pathogenesis of Atherosclerosis : Video Animation

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