A brief powerpoint presentation on one of the most talked about health concerns today- Atherosclerosis

1. ATHEROSCLEROSIS
27/02/2012
Supervisor- Dr. Ndungú
Presenter- Taseer Feroze Din

2. OBJECTIVES
 Introduction
 Definition
 Epidemiology
 Risk factors
 Pathogenesis
 Response-to-injury Hypothesis
 Complications

3. INTRODUCTION
 Definition :
Atherosclerosis (art
eriosclerotic
vascular disease) is
a condition in which
an artery wall
thickens as a result
of the accumulation
of fatty materials
such as cholesterol.
 In
Greek, athere means
gruel, and skleros
means hard.

4. EPIDEMIOLOGY- UBIQUITOUS AMONG MOST DEVELOPED
NATIONS...’’LIFESTYLE AND DIET DISEASE’’
MAJOR RISKS LESSER OR UNCERTAIN
RISKS Multiplicative
Nonmodifiable Obesity effect:
•2 risk factors
•Increasing age Physical inactivity
increase risk
•Male gender Stress (type A personality) fourfold
•Family History Postmenopausal estrogen •3 risk factors
def. increase the
•Genetic Abnormalities High Carbohydrate intake rate of MI seven
Potentially Controllable Lipoprotein (a) times!
•Hyperlipidemia Hardened (trans)
unsaturated fat intake
•Hypertension Chlamydia pneumoniae
infection
•Cigarette smoking
•Diabetes
•C-reactive protein

5. ATHEROSCLEROSIS IN AFRICA
 CVD now the second most common cause of death-
accounting for 11% of total deaths (WHO 1999)
 Projections from the Global Burden of Disease Project
suggest that from 1990 to 2020, the burden of CVD
faced by African countries will double.
 In a prospective study among elderly patients in
Kenyatta National Hospital, Nairobi, Kenya, in 1991
to 1992:
 Clinical evidence of CVD was present in 40% of the
patients evaluated;
 54% were hypertensive,
 53% had arrhythmia, and
 49% CCF (Lodenyo, McLigeyo, and Ogola 1997)

6. PATHOGENESIS

7. 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

8. RESPONSE-TO-INJURY HYPOTHESIS
1) CHRONIC
ENDOTHELIAL INJURY
:
 Hyperlipidemia
 Hypertension
 Smoking
 Homocysteine
 Hemodynamic factors
 Toxins
 Viruses
 Immune Reactions

9. 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 dysfunction underlies human
atherosclerosis; in the setting of intact but
dysfunctional ECs :
 increased endothelial permeability
 enhanced leukocyte adhesion
 altered gene expression.

10. 2) ACCUMULATION OF LIPOPROTEIN
IN VESSEL WALL  Dyslipoproteinemia
 Other underlying disorder
that affects 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)

11. HYPERLIPIDEMIA-MAJOR RISK FACTOR
 The mechanisms :
 Chronic hyperlipidemia, particularly
hypercholesterolemia - increases local production of
reactive oxygen species-accelerate nitric oxide decay-
local shear stress.
 Lipoproteins accumulate within the intima-
oxidized through the action of oxygen free radicals
(locally generated by macrophages or ECs) Oxidized
LDL is ingested by macrophages through a scavenger
receptor, resulting in foam-cell formation.
 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.

12. 3) MACROPHAGE AS THE INFLAMMATORY
MEDIATOR
Monocyte adhesion
to the endothelium,
followed by
migration into the
intima and
transformation
into macrophages
and foam cells.

13. INFLAMMATION
 Dysfunctional arterial ECs express VCAM-1- binds
monocytes and T cells-migrate- chemokines.
 Monocytes transform into macrophages and avidly
engulf lipoproteins, including oxidized LDL. –Activated-
cytokine production (e.g., TNF)-propel mononuclear
inflammatory cell recruitment.
 T lymphocytes recruited to the intima- elaborate
inflammatory cytokines, (e.g., interferon-γ), which in
turn can stimulate macrophages as well as ECs and
SMCs.
 Activated leukocytes and vascular wall cells release
growth factors that promote SMC proliferation and
ECM synthesis.

14. 4) SMC PROLIFERATION AND
ECM PRODUCTION  Intimal SMC proliferation and
ECM deposition convert a fatty
streak to a mature atheroma.
 Intimal SMC-proliferative,
synthetic phenotype
 Growth factors:
1. PDGF (platelets,
macrophages, ECs, and
SMCs)
2. FGF
3. TGF α.
 SMCs synthesize ECM (notably
collagen), which stabilizes
atherosclerotic plaques.
 Inflammatory cells in atheromas
can cause intimal SMC
apoptosis, and they also
increase ECM catabolism,
resulting in unstable plaques.

16. 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
 Arrthymias- due to scar formation
 Mural thrombus
 Atheroembolism- microemboli
 Cerebral infarct
 Renal infarcts
 Death

17. NATURAL HISTORY, MAIN PATHOGENIC EVENTS
& CLINICAL COMPLICATIONS

18. THANK YOU ARMY A1