Atherosclerosis

By
Deepak Raj
 Atherosclerosis
• Atherosclerosis underlies the pathogenesis of coronary ,
cerebral and peripheral vascular disease and causes
morbidity and mortality
• Intimal lesions called atheromas ( atheromatous or
atherosclerotic plaques) that protrude into vessel lumens
are formed.
• An atheromatous plaque consist of raised lesion with a
core of lipid covered by a fibrous cap.
• It obstructs blood flow and increase the diffusion distance
from the lumen to the media causing obstructive vascular
thrombosis and ischemic injury respectively.
Epidemiology

 Reduced mortality from infectious diseases and

the adoption of Western lifestyles has led to
increased prevalence of ischemic heart disease in
developing nations
 As a result the death rate of coronary disease in
the USA now lacks behind the death rate in most
of Africa, India and southeast Asia
Constitutional risk factors

 Genetics – familial hypercholesterolemia

 Age – between ages 40 and 60
 Gender – premenopausal women are relatively
protected against artherosclerosis comparative
men
Modifiable major risk factor

 Hyperlipidemia
 Hypercholestrolemia (increased LDL and decresed
HDL) is sufficient to initiate lesion development
even in the absence of other risk factors
 HDL(good cholesterol) levels are lowered by obesity
and smoking whereas the levels are increased by
exercise
 Statins
are a class of drugs that lower circulating
cholesterol level by inhibiting HMG CoA reductase,
the rate limiting enzyme in cholesterol biosynthesis
 Hypertension
 Cigarette smoking
 Diabetes mellitus
 Inflammation – C reactive protein(CRP) has
emerged as one of the simplest to measure and
one of the most sensitive
 hyperhomocystinemia
 Metabolic syndrome
 Lipoprotein A – its levels are associated with
coronary and cerebro vascular disease
risk,independent of total cholesterol levels.
Pathogenesis
 Endothelial injury and dysfunction
 Increased vascular permeability, leukocyte adhesion and
thrombosis

 Accumulation of lipoprotein
 Monocyte adhesion to the endothelium
 Transforms into macrophages and foam cells

 Platelet adhesion
 Factor release
 Smooth muscle cell recruitment

 Smooth muscle cell proliferation, extracellular matrix

production and recruitment of T cells
 Lipid Accumulation
 Both extracellularly and within macrophages and smooth muscle
cells
HYPERLIPIDEMIA
 Impairs endothelial cell function by increasing local
reactive oxygen providing species production.
 They cause membrane and mitochondrial damage and
accelerate nitric oxide decay
 They also oxidise lipoproteins that accumulate within the
intima
 Such modified LDL is then accumulated by macrophages
and smooth muscle cells
 Chronic ingestion into these cells leads to the formation
of foam cells
Atherosclerotic plaque
 They are white yellow and encroach on the lumen
of the artery.
 They are patchy and eccentric
 Local vascular flow disturbances ( turbulence at
branch points)
 In descending order the most extensively involved
vessels are
 Lower abdominal aorta
 Coronary artery
 Popliteal artery
 Internal carotid artery
 Vessels of circle of Willis
Consequences of atherosclerotic
diseases
 Acute plaque change
Rupture or fissuring – exposes thrombogenic
plaque constituents
Erosionor ulceration – exposes thrombogenic
sub endothelial basement membrane
Hemorrhage into the atheroma – expands its
volume
 Production of Collagen in the fibrous cap is
controlled by metalloproteinases (MMP).It is
inhibited by tissue inhibitors of
metalloproteinases (TIMP)
 Vulnerable plaque
They have thin fibrous caps or
contain few smooth muscle cells or
have clusters of inflammatory cells
 Stable plaque
They have thick fibrous cap