ATHEROSCLEROSIS

Definition :
Atherosclerosis is characterized by intimal lesions calld
atheromatous plaques consist of a raised focal plaque having a
core of lipid (mainly cholesterol and cholesterol esters) and a
covering fibrous cap.
Symptomatic atherosclerotic disease most often involves the
arteries supplying the heart, brain, kidneys and lower
extremities.

Classification of Human Atherosclerotic lesions

Type I
- Isolated macrophage foam cells (fatty dots).
- Clinically silent
Type II
- "Fatty streak" lesion
- First decade
Type III
- Type II + small extra-cellular lipid pools.
- 3rd decade
- Clinically silent
Type IV
- "Atheroma" lesion
- Silent or overt
Type V
- "Fibroatheroma" lesion 4th decade.
- lipid core + fibrotic layer + smooth muscle.
- 4th decade
Type VI
- Complicated lesion
- Fourth decade
- Surface defect
- Thrombosis, haematoma and hemorrhage

Morphology :
Sites : Aorta, carotid and iliac arteries. Coronary and popliteal
arteries. Internal carotid A and vessels of circle of willis.
Atheromatous plaques appear white to whitish yellow and impinge
on the lumen of the artery.
3 principal components of atherosclerotic plaques:
1. Cells - Foam cells, SMCS, mac. and leucocytes.
2. ECM - collagen, elastin, proteoglycans
3. Intracellular and extra-cellular lipid.
Foam cells: Large lipid-laden cells that derive from tissue
macrophages but SMCs can also imbibe lipid to become foam
cells.

Epidemiology and risk factors:

Major Risk factors
Non modifiable
Increasing age : 40-60yrs incidence increases five fold.
Male gender Family history
Genetic abnormalities- Familial hyper cholesterolemia
D.M
hypertension
Lesser or uncertain
Obesity Physical inactivity Stress ("Type A" personality)
Postmenopausal estrogen deficiency
High carbohydrate intake

Major Risk factors

Potentially Controllable
Hyperlipidemia - LDL
HDL(good cholesterol)
- Smoking and obesity is responsible.
Hypertension- 45-62 yrs. B.P: 169/95mmHg five
fold greater risk.
Cigarette smoking
D.M. induces hypercholesterolemia
Lesser, Uncertain factors:
Alcohol, Homocystinuria, Chlamydia pneumonia
Hardened (trans) unsaturated fat intake, Lipoprotein Lp (a)

PATHOGENESIS:
The role of chronic endothelial injury with endothelial dysfunction
Chronic endo. injury :
Hyper lipidemia Hypertension Smoking Homocysteine
Hemodynamic disturbances Toxins Viruses Immune reactions.
But early human lesions begin at sites of intact endothelium. Non
denuding endothelial dysfunction causing increased endothelial
permeability, enhanced leucocyte adhesion and emigration.
Infectious agents : Cytokines e.g. TNF stimulate expression of
endothelial genes that may promote atherosclerosis.

The Role of Inflammation:

Inflammatory mechanisms initiate to express on their surface
selective adhesion molecules that bind different types of leucocytes
such as monocytes and T lymphocytes.
Monocytes: Adhere to the endothelium, migrate between ECS,
transform into macrophages and engulf oxidized LDL.
Mac. produce IL-1 and TNF- increased adhesion of leucocytes.
- toxic oxidation species that
causes oxidation of lipids
- G.F produce SMC proliferation
T cells- Produce INF- can stimulate mac, vascular endothelial cells
and SMCs.

The Role of Lipid

Lipoproteins complexed to specific apoproteins and are transported.
Dyslipiderma - mutations lead to defective apolipoproteins
- N.S., alcoholism, hypothyroidism
- D.M.
Lipoproteins abnormalities -

LDL
HLD
abnormal lipoprotein Lp (a)

The Role of SMC

G.F.

- PDGF, FGF and TGF- - proliferation of SMCs.

- SMCs may also take up modified lipis contributing
"FOAM Cell" formation.
- SMCs synthesize collagen that stabilize plaques.

Aneurysm
An aneurysm is a localized abnormal dilation of a blood vessel
or the wall of the heart.
Types of Aneurysm (Formation): True aneurysm : An aneurysm bounded by arterial wall
components or the attenuated wall of the heart.
Atherosclerotic, syphilitic, congenital vascular aneurysms
and left ventricular aneurysms following a M.I.
False aneurysm : (Pseudoaneurysm) = A breach in the
vascular wall leading to an extravascular hematoma that freely
communicate with the intravascular space.
Post M.I rupture contained by a pericardial adhesion.

Types (Macroscopic shape and size):

Saccular Fusiform
Aortic Aneurysms
Atherosclerosis Cystic medial degen of the media
Abdominal Aortic Aneurysm:
Site : Ab. Aorta - below the renal arteries and above the
bifurcation of the aorta.
- Saccular or fusiform
- Atheromatous ulcer and mural thrombi.
- Detached atheroemboli may lodge in
the vessels of the kidneys or lower extemitis.

Pathogenesis :
-

Atherosclerosis

Male predominance and 5th decade

Genetic susceptibility

- Recently altered balance of collagen

degradation and synthesis mediated by local
inflammatory infiltrates and the destructive
proteolytic enzymes they produce.
- MMPs have role and in patients with
aortic aneurysms level ofTIMP have been
reported.