1. VASCULAR DISEASE Atherosclerosis Jagdish Butany,MBBS,MS,FRCPC, Prof. Dept Lab Med & Pathobiol., Pathologist, UHN-Toronto Gen/Hosp 416 340 3003 jagdish.butany@uhn.on.ca Fac. Pharmacy Nov ‘07.

2. Vascular disease 1. Atherosclerosis 2.Degenerative disease 3.Collagen vascular diseases 4.Tobacco related disease- T.A.O./Buergers

3. J. Butany ATHEROSCLEROSIS Atheros: Soft gruel-like Scleros: Hardening

4. Atherosclerosis A chronic disease of elastic and large and medium sized arteries.

5. Arterial Wall Intima- lined by endothelial cell layer Media - muscle and elastic tissue Adventitia- collagen, elastic fibers small vessels (Vasa Vasorum)

6. Atherosclerosis “Disease” of the intima Secondary damage to media Adventitia - generally uninvolved

7. Atherosclerosis The root of ALL (almost ??) Cardiovascular Evil!!

8. Ischemic Heart Disease The SCOURGE of Affluent Societies- ? 50% of Deaths Even more Significant : MORBIDITY

9. Atherosclerosis Risk Factors: ?? N.B. * Increase risk x4.

10. Atherosclerosis Risk Factors: Age Cigarette Smoking* Gender Elevated homocysteine Genetics (plasma) Lipids-hyperlipidemia* Other Factors Hypertension* Lack of Exercise Stress Weight gain [Alcohol- Beneficial effect High intake of cholesterol/ Saturated fats ?Acclerating factors? N.B. * Increase risk x4.

11. Endothelial Cells – Complex Functions Lining of Cardiovascular System Homeostasis Nonthrombogenic Surface Multifunctional Tissue “Mechanical” function Regulate vascular tone Regulate Immune/Inflammatory Reactions. “Synthetic” Function “Metabolic” Function Semipermeable membrane Thrombosis/Thrombolysis Initiate atherosclerosis

12. Endothelial Cells Molecular/Gene Changes Adhesion molecules Cytokines/Chemokines Growth factors Vasoactive peptides MHC molecules Coagulation factors Others [Nuclear factor |< B (NF - |<B)

13. Atherosclerosis-Theories Pathogenesis: Response to Injury Basis: Focal, chronic endothelial injury Endothelial Dysfunction Insudation of Lipoprotein Adhesion of Blood Cells Platelets Macrophages Migration of Smooth Muscle Accumulation of Lipid Role of Hemodynamics

14. Atherosclerosis Lesions Incidence:Aorta Coronaries Popliteal Internal carotid Circle of Willis

15. Atherosclerosis Lesions Site: Abdominal>Thoracic Bifurcation>Rest of Aorta Branch points>Straight segments

16. ATHEROSCLEROSIS Lesion: 1. Raised intimal “plaque” Lipid core Fibrous cap On the IEL/Media 2. Fatty, fibrous, Fibrofatty Lipid, Fibrolipid Complex

17. Atherosclerotic Plaque Composition: Varies with age Mature plaque Cells Connective tissue Lipid-intra/extra cellular [cholesterol/esters]

18. Atherosclerotic Plaque Complications: Rupture and/or ulceration Plaque Hemorrhage Thrombosis Calcification

19. Atherosclerosis Endothelial injury: 1. Repetitive denuding injury - thrombus - repair - atheroma 2. “Non-denuding” injury - E. dysfunction

20. Hypertension Common problem Easily diagnosed Easily treated (not cured) - 90% Asymptomatic - Long periods BP High:Diastolic > 90 mmHg Systolic > 140 mmHg Incidence: 25% Black people 2x > Caucasians

21. Hypertension Malignant hypertension Secondary hypertension