PATHOGENESIS

Of Atherosclerosis
SANIYYA AHMED
2nd YEAR M.Sc. NURSING
AMRITA COLLEGE OF NURSING
AIMS / KOCHI
Introduction
Definition: Atherosclerosis (art eriosclerotic
vascular disease) is a condition in which
an artery wall thickens as a result of the
accumulation of fay materials such a s
cholesterol.
● In greek, athere means gruel, and skleros
means hard.
Pathogenesis
• Response-to-injury hypothesis- 4 main
stages to atherogenesis:
1 . Chronic endothelial injury
2 . Accumulation of lipoproteins
3 . Resultant Inflammation & Factor release
4 . Smooth muscle cell recruitment, proliferation
and ECM production
Chronic endothelial injury
● Hyperlipidemia: elevated concentrations
of lipids or fats within the blood.
● Hypertension: blood pressure that is
higher than normal.
● Smoking
● Homocysteine:is a type of amino acid
that your body naturally makes. At high
levels, it can damage the lining of arteries.
1. Chronic endothelial injury
● Hemodynamic factors: The factors
influencing hemodynamics are extensive
and include circulating fluid volume,
respiration, vascular diameter and
resistance, and blood viscosity.
● Toxins
● Viruses
● Immune reactions
Endothelial injury
● Intimal thickening; in the presence of
high- lipid diets, typical atheromas ensue.

● Early human lesions begin at sites of

morphologically intact endothelium.
Endothelial injury
● Endothelial dysfunction underlies human
atherosclerosis; in the seing of intact
but dysfunctional ECs :

- increased endothelial permeability

- enhanced leukocyte adhesion
- altered gene expression.
2. Accumulation of Lipoprotein
● Dyslipoproteinemia
● Other underlying disorder
● that aects the circulating
levels of lipids:
- nephrotic syndrome,
alcoholism, hypothyroidism, or
diabetes mellitus

● (1) increased LDL cholesterol

levels,
● (2) decreased HDL cholesterol
levels, and
● (3) increased levels of the
abnormal Lp(a)
Hyperlipidemia- Major risk factor
The mechanisms
● Chronic hyperlipidemia, particularly
hypercholesterolemia - increases local
production of reactive oxygen
species-accelerate nitric oxide decay-
local shear stress.
Hyperlipidemia- Major risk factor
● in addition, oxidized LDL stimulates the
release of growth factors, cytokines, and
chemokines by ECs and macrophages
that increase monocyte recruitment into
lesions.
● Finally, oxidized LDL is cytotoxic to ECs
and SMCs- EC dysfunction.
3. Macrophage as the inflammatory
mediator
Monocyte adhesion to the
endothelium, followed by
migration into the intima
and macrophage
transformation
Inflammatory cytokines,
chemokines, proteases,
radicals
into macrophages and
foam cells
Inflammation
● Dysfunctional arterial ECs express
VCAM-1- binds monocytes and T cells
-migrate- chemokines.
● Monocytes transform into macrophages
and avidlye ngulf lipoproteins, including
oxidized LDL. -Activated cytokine
production (e.g., TF)-propel mononuclear
inflammatory cell recruitment.
Inflammation
● T lymphocytes recruited to the
intima-elaborate inflammatory cytokines,
(e.g., interferon-), which in turn can
stimulate macrophages as well as ECs
and SMCs.
● Activated leukocytes and vascular wall
cells release growth factors that promote
M C proliferation and ECM synthesis.
 ● Intimal SMC proliferation and ECM deposition
SMC proliferation and ECM
convert a fay streak to a mature atheroma.
production
● Intimal SMC-proliferative, synthetic
phenotype
Growth factors:
1. PDGF (platelets, macrophages, ECs, and
a
SMCs) t iti dia ima
n e Int
ve M
2. FGF A d

3. TGF a.
● SMCs synthesize C M (notably collagen),
which stabilizes atherosclerotic plaques.
● Inflammatory cells in atheromas can cause
intimal SMC apoptosis and they also
increase ECM catabolism resulting in
 SMC proliferation and ECM
production
● Intimal SMC proliferation and entitia edia tima
v M In
ECM deposition convert a Ad

fay streak to a mature

atheroma.
● Intimal SMC-proliferative,
SMC proliferation and ECM
production
a
t iti dia ima
Growth factors: d ven Me Int
A
1. PDGF (platelets,
macrophages, ECs, and
SMCs)
2. FGF
3. TGF a.
SMC proliferation and ECM
production
● SMCs synthesize C M a
iti dia ima
(notably collagen), which ven Me Int
t
d
stabilizes atherosclerotic A
plaques.
● Inflammatory cells in
atheromas can cause intimal
SMC apoptosis and they also
increase ECM catabolism
resulting in unstable plaques.
Complications
● MI
● Rupture, Ulceration, or Erosion:
thrombus formation-downstream
ischaemia
● Aneurysm: pressure or ischaemic
atrophy of the underlying media, with loss
of elastic tissue- weakness
● Arrhythmias: due to scar formation o
● Mural thrombus
Complications
● Atheroembolism: microemboli
● Cerebral infarct
● Renal infarcts
● Death
Natural history, Main pathogenic
events & clinical complications.