1. Atherosclerosis
Dr:HAMED ALGHAMDI

2. Atherosclerosis is a systemic disease of large and medium sized arteries in which lipid and fibrous material accumulate within the intimal layer.
The word atherosclerosis is derived from two Greek roots: (athere, gruel) and (skleros, hard).
Hardening of the arteries.

3. It should not be confused with the more general term arteriosclerosis, which refers to generalized
thickening and loss of elasticity of arteries as a result of an increased amount of basement material and plasma protein deposition.

4. Histologically, the arterial wall consists of three distinct layers:
1-the intima (endothelium and subendothelial space)
2-the media (smooth muscle cells [SMCs])
3-the adventitia (vasa vasorum and connective tissue elements).
The intima consists of the endothelium, its basement membrane, and the subendothelial space, which extends to the internal elastic laminae.
The endothelium is a single layer of cells lining the inner surface of all blood vessels.

8. The endothelium is an organ with autocrine, paracrine, and endocrine functions that serve to regulate blood vessel tone and thrombogenicity.
The endothelium synthesizes many factors that regulate vascular tone (e.g., nitric oxide [NO], hyperpolarizing factors, prostaglandins, endothelin, angiotensin II) and interactions with blood elements (e.g., adhesion molecules, thrombomodulin, plasminogen activators), which all work in balance to maintain vascular homeostasis.

9. Endothelial dysfunction is regarded as the earliest manifestation of vessel injury and is present before histologic evidence of atherosclerosis.
The subendothelial space is particularly relevant in atherosclerosis because it is the location where atherogenic particles are retained and modified so that they can be taken up by macrophages and SMCs.
The vasa vasorum may contribute to atherosclerosis as well.

10. The atherosclerosis begins early in life, and associated with risk factors, and occurs in anatomical location susceptible to the formation of more advanced fibrous plaque.
Atherosclerosis is now recognized as an inflammatory disease, and components of the innate and adaptive immune system are involved in every step of the atherosclerotic process.

11. Clinically, cholesterol is an established causative risk factor for atherosclerosis.
The cholesterol leads to vascular inflammation by activating the immune system.
Cells of innate immunity are equipped with receptors that detect pathogen-associated molecular patterns and endogenous danger signals
Once these receptors are activated, monocytes and macrophages secrete inflammatory cytokines.

12. Anatomical location:
The propensity of atherosclerosis to occur at specific sites in the arterial tree has been observed since long time.

13. Areas of well developed laminar shear stress are relatively resistant to atheroma formation, whereas areas of turbulent or low shear stress (such as the carotid bifurcation) are more susceptible to atherosclerosis.
Branch points, bifurcations, and major curvatures disrupt laminar flow and cause boundary layer separation, flow reversal, and shifting stagnation points.

14. Risk Factors of atherosclerosis:
Modifiable
Non Modifiable

16. Putting It All Together: The Inflammasome

17. 1- endothelial dysfunction;
2- vascular smooth muscle cell hypertrophy;
3- migration and proliferation of vascular smooth muscle cells;
4- matrix elaboration;
5- expression of adhesion molecules and migration of monocytes;
6- uptake of low-density lipoprotein (LDL) and formation of foam cells;
7- thrombus formation;
8- angiogenesis and neovascularization.

20. What is the clinical consequence of atherosclerosis:
Stable plague
Vulnerable plague

26. Much of the practice in vascular surgery is driven by the detection of flow-limiting stenosis
It is thought that physical disruption of the atherosclerotic plaque rather than critical stenosis can commonly precipitate arterial thrombosis.

27. Four mechanisms of plaque disruption may cause thrombosis or rapid plaque expansion
complete fracture of the plaque’s fibrous cap causes most cases of fatal coronary thrombosis
Inflammation within the plaque may destabilize the cap and potentiate injury by hemodynamic factors
Macrophages and mast cells degrade extracellular matrix by phagocytosis and secretion of proteolytic enzymes

28. Intraplaque hemorrhage can transform an asymptomatic carotid plaque into a symptomatic lesion and produce transient ischemic attacks or stroke.
Erosion through the intima of a calcified nodule represents another less common form of atherosclerotic thrombosis that may be relevant in both the coronary and peripheral circulations.

29. Once the plaque is fractured, blood is exposed to the underlying thrombogenic substrate and thrombosis ensues.
Tissue factor initiates the extrinsic clotting cascade and is a major regulator of coagulation and thrombosis.

30. THANK YOU