1. Arteriosclerosis & Atherosclerosis
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied University

2. Arteriosclerosis
= hardening of arteries = arterial wall thickening + loss of elasticity …3 types: -Arteriolosclerosis -Monckeberg medial sclerosis -Atherosclerosis

3. Arteriosclerosis, cont’d
Arteriolosclerosis, 2 types:
Hyaline
Hyperplastic
…Both may cause ischemia
Monckeberg medial sclerosis:
- Calcific deposits in muscular arteries
With age older than 50 years
Clinically not significant

4. Atherosclerosis characterized by
-intimal lesions called atheromas (or atheromatous or atherosclerotic
plaques)
…Atheromatous plaques are: raised lesions composed of soft lipid cores
(mainly cholesterol and cholesterol esters, with necrotic debris)
covered by fibrous caps

5. Atherosclerosis, epidemiology
CAD (IHD) and atherosclerosis
Developed more than developing
USA more than Japan…but increasing now in Japan
Vessels?

6. Atherosclerosis, risk factors
-High dietary intake of cholesterol and saturated fats
(present in egg yolks, animal fats, and butter, for
example) raises plasma cholesterol levels. Conversely,
diets low in cholesterol, and/or containing higher
ratios of polyunsaturated fats, lower plasma cholesterol
levels.
-Omega-3 fatty acids (abundant in fish oils) are beneficial,
whereas (trans)-unsaturated fats produced by
artificial hydrogenation of polyunsaturated oils adversely affect cholesterol profiles.
-Exercise and moderate consumption of ethanol raise HDL levels, whereas obesity and smoking lower them.
-Statins are a widely used class of drugs that
lower circulating cholesterol levels by inhibiting hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis
…The most important
…e.g., familial hypercholesterolemia
…small percentage of the cases but
strongly associated
…AD
…mostly polygenic (when associated
with HTN, DM..etc.)
> 40
20%: no identified risk factors
…For example, in previously
healthy women more than 75% of cardiovascular events occur in those with LDL cholesterol levels below 160 mg/dL (a cut-off value generally considered to connote low
risk)
Increases cholesterol

7. Atherosclerosis risk factors, cont’d
Inflammation is very important and present in all stages
…so CRP level is important
CRP levels strongly and independently predict the risk of myocardial infarction, stroke, peripheral arterial disease, and
sudden cardiac death, even among apparently healthy persons
Also locally, CRP secreted by cells within atherosclerotic plaques can activate endothelial cells, increasing adhesiveness
and inducing a prothrombotic state
CRP is reduced by smoking cessation, weight loss, and exercise
statins reduce CRP levels independent
of their LDL cholesterol-lowering effects, suggesting a possible anti-inflammatory action of these agents

8. Atherosclerosis risk factors, cont’d
Hyperhomocysteinemia
…Homocystinuria, due to rare inborn errors of metabolism
…early-onset vascular disease
…although low folate and vitamin B12 levels can increase homocysteine, supplemental vitamin ingestion does not affect the incidence of cardiovascular disease
Metabolic syndrome:
Insulin resistance
hypertension
dyslipidemia (elevated LDL and depressed HDL)
hypercoagulability
Proinflammatory state

9. Atherosclerosis risk factors, cont’d
Lipoprotein(a) levels
…an LDL-like particle…apolipoprotein B-100 linked to apolipoprotein A
Elevated levels of procoagulants
…thrombin initiates inflammation through cleavage of protease-activated receptors (PARs) on leukocytes, endothelium, and other cells, may be particularly atherogenic
lack of exercise and living a competitive, stressful life style (“type A personality”)

10. Atherosclerosis, pathogenesis
Hemodynamic disturbances are very important
…plaques tend to occur at ostia of exiting
vessels, at branch points, and along the posterior wall of the abdominal aorta, where there is turbulent blood flow
-increased LDL cholesterol levels
-decreased HDL cholesterol levels
-Increased levels of lipoprotein(a)
nephrotic syndrome, alcoholism, hypothyroidism, or diabetes mellitus…are causes of abnormal lipid metabolism

11. Atherosclerosis, pathogenesis
Chronic hyperlipidemia, particularly hypercholesterolemia:
-impaired endothelial cell function by increasing local oxygen free radical production
…also oxygen free radicals accelerate NO decay, damping its vasodilator activity
-lipoproteins accumulate within the intima, where they are hypothesized to generate two pathogenic
derivatives,
oxidized LDL and cholesterol crystals.
-LDL is oxidized through the action of oxygen free radicals generated locally by macrophages or endothelial cells
and ingested by macrophages through the scavenger receptor, resulting in foam cell formation.
-Oxidized LDL stimulates the local release of growth factors, cytokines, and chemokines, increasing
monocyte recruitment, and also is cytotoxic to endothelial cells and smooth muscle cells

12. Atherosclerosis, pathogenesis
Dysfunctional endothelial cells…more adhesion to WBCs and more inflammation
Engulfment of lipids by macrophages…more activation of WBCs and more oxidation of LDL
T cells interact with macrophages…chronic inflammation
…the result of released mediators is: proliferation of smooth muscle &
deposition of ECM in the intima
…PDGF, TGF-alpha & FGF…proliferation of SM cells
…this will convert the lesion from fatty streak to atheroma

13. Atherosclerosis, morphology
1- Fatty streaks: -minute yellow, flat macules that coalesce into elongated lesions, 1 cm or more in length -composed of lipid-filled foamy macrophages but are only minimally raised and do not cause any significant flow disturbance -although fatty streaks may evolve into plaques, not all are destined to progress -Fatty streaks can appear in the aortas of infants younger than 1 year of age and are present in virtually all children older than 10 years

14. 2- Atherosclerotic Plaque

15. Atherosclerotic plaques have three principal components:
(1) cells, including smooth muscle cells, macrophages, and T cells
(2) extracellular matrix, including collagen, elastic fibers, and
proteoglycans
(3) intracellular and extracellular lipid

16. Overview

17. Clinical consequences of atherosclerosis
Ischemia and aneurysms
Mainly large elastic arteries (aorta, carotid and iliac) and muscular arteries
Risk of rupture depends on multiple factors

18. Thank You