1. Associate professor of pathology
ATHEROSCLEROSIS By
Dr. Abdelaty Shawky
Associate professor of pathology

2. Histology of the vascular wall
Diagrammatic representation of the main components of the vascular wall, seen here in a muscular artery.

3. Endothelial cells
Single cell-thick, continuous lining of the entire cardiovascular system, collectively called the endothelium.
Endothelial structural and functional integrity is fundamental to the maintenance of vessel wall homeostasis and normal circulatory function.

4. Smooth muscle cells
SMCs are predominant cellular element of the vascular media
SMCs are responsible for vasoconstriction and dilation in response to normal or pharmacologic stimuli.
SMCs are important elements of both normal vascular repair and pathologic processes such as atherosclerosis

5. Arteriosclerosis
Arteriosclerosis literally means "hardening of the arteries”. It is a term for thickening and loss of elasticity of arterial walls. Three patterns are recognized: 1. Atherosclerosis: the most frequent and important pattern. 2. Mönckeberg medial calcific sclerosis: is characterized by calcific deposits in muscular arteries in older people. 3. Arteriolosclerosis: affects small arteries and arterioles. Is seen with hypertension and diabetes mellitus.

6. Atherosclerosis
* Definition: Generalized, degenerative arterial disease characterized by patchy thickening of the intima by atheromas, which protrude into and obstruct vascular lumens and weaken the underlying media.

7. * Risk factors for atherosclerosis:
I. Non-modifiable risk factors:
Genetic predisposition: Family history is the most important independent risk factor for atherosclerosis. Certain genetic disorders are strongly associated with atherosclerosis e.g., familial hypercholesterolemia.
Age: Atherosclerosis manifests in middle and old ages.
Gender: Atherosclerosis is less common in pre-menopausal females than males, however is more common in post-menoapsual females than males.

8. II. Modifiable risk factors:
Hyperlipidemia.
Hypertension.
Cigarette smoking.
Diabetes.

9. Hyperlipidemia and, more specifically, hypercholesterolemia—is a major risk factor for development of atherosclerosis and is sufficient to induce lesions in the absence of other risk factors. The main cholesterol component associated with increased risk is low-density lipoprotein (LDL) cholesterol (“bad cholesterol”); LDL distributes cholesterol to peripheral tissues.

10. By contrast, high-density lipoprotein (HDL) (“good cholesterol”) mobilizes cholesterol from developing and existing vascular plaques and transports it to the liver for biliary excretion.
Consequently, higher levels of HDL correlate with reduced risk.

11. * Pathogenesis of atherosclerosis:
Response to injury hypothesis:
It considers atherosclerosis to be a chronic inflammatory response of the arterial wall initiated by injury to the endothelium.

12. 1. Chronic endothelial injury induced by:
- Hypertension, Hyperlipidaemia, Cigarette smoking….etc.
This leads to endothelial dysfunction (increased permeability to cholesterol, leukocyte adhesion.
2. Accumulation of lipoproteins: mainly LDL
in the vessel wall.

13. 3. Adhesion of blood monocytes to the endothelium, followed by their migration into the intima and their transformation into macrophages which engulfs the entering cholesterol and becomes foam cells.
4. Adhesion of platelets to the exposed sub-intimal collagen.
5. Smooth muscle cell recruitment to the intima due to release of mitogenic growth factors from activated platelets and foam cells.

14. 6. Proliferation of smooth muscle cells in the intima, and elaboration of extracellular matrix, leading to the accumulation of collagen and proteoglycans.

15. Chronic endothelial “injury” theory
Slide 12.13

16. 2
Endothelial dysfunction
Monocyte adhesion and emigration

17. 3 How to Make an Atheroma Macrophage activation
Smooth muscle recruitment

19. 5, Well-developed plaque.

20. * Gross and microscopic morphology:
1. Fatty spots: are the earliest lesion of atherosclerosis as multiple yellow, flat spots less than 1 mm in diameter. They are composed of lipid-filled foam cells.
2. Fatty streaks: fatty spots coalesce into elongated streaks, 1 cm long or longer. They are not significantly raised and thus do not cause any disturbance in blood flow.

21. Fatty streak—a collection of foam cells in the intima
Photomicrograph of fatty streak in an experimental hypercholesterolemic rabbit, demonstrating intimal macrophage-derived foam cells ( arrow).
Aorta with fatty streaks ( arrows).

22. 3. Atheroma (atherosclerotic plaque): consists of raised patches within the intima, having a soft, yellow, core of lipid, covered by a firm, white fibrous cap.

23. * Microscopically:
Atherosclerotic plaques have three principal components:
1. Cells, including smooth muscle cells (SMCs), macrophages, and other leukocytes
2. Extracellular matrix(ECM), including collagen, elastic fibers, and proteoglycans
3. Lipid (LDL): intracellular (foam cells) and extracellular (crystals)..

24. The previously mentioned components are arranged in these layers :
1. Fibrous cap: in the top composed of SMCs and relatively dense ECM, macrophages, and lymphocytes. 2. Necrotic core: Deep to the fibrous cap , containing cholesterol clefts, necrotic debris from dead cells, foam cells and fibrin.

25. * Sites of atherosclerosis:
Large elastic arteries e.g., aorta, carotid, and iliac arteries.
Large and medium-sized muscular arteries e.g., coronary, renal, and popliteal arteries are the vessels most commonly involved by atherosclerosis.

26. * Complications:
1. Rupture, ulceration, or erosion of the luminal surface of atheromatous plaques.
2. Atheroemboli.
May occur after rupture of atheromatous plaque which may be fragmented into microemboli.

27. 3. Hemorrhage into a plaque may be initiated by rupture of either the overlying fibrous cap or the thin-walled capillaries that vascularize the plaque. A contained hematoma may expand the plaque or induce plaque rupture. 4. Thrombosis usually occurs on disrupted lesions (those with rupture, ulceration, erosion, or hemorrhage) and may partially or completely occlude the lumen.

28. 5. Aneurysm: is abnormal dilatation of the arterial wall which is induced by atrophy of the underlying media, with loss of elastic tissue, causing weakness, and potential rupture 6. Calcifications: Atheromas often undergo calcification.

29. Please take care of atherosclerosis