Atherosclerosis

Latha Karuniathi

Farith

Maariah Qibtiah

Definition Atherosclerosis: disease primarily of elastic

arteries and large/medium sized muscular arteries. It is characterized by the presence of intimal lesions called atheromas (or atheromatous or atherosclerotic plaques).

Atheromatous plaques are raised lesions composed of soft grumous lipid cores (mainly cholesterol and cholesterol esters, with necrotic debris) covered by fibrous caps

Atherosclerotic plaques can mechanically obstruct vascular lumina and are prone to rupture, resulting in catastrophic vessel thrombosis.

Risk factors Age Male gender Family history Genetic abnormalities Hyperlipidemia Hypertension Cigarette smoking Diabetes Obesity Physical inactivity Hardened unsaturated fat intake

Pathogenesis

Response-to-injury hypothesis, the model views atherosclerosis as a chronic inflammatory response of the arterial wall to endothelial injury.

Lesion progression involves interaction of modified lipoproteins (oxidized lipoprotein), monocyte-derived macrophages, T lymphocytes, and the cellular constituents of the arterial wall.

Response-to-injury hypothesis

1. Cell injury2. Accumulation of lipoproteins (mainly oxidized LDL and cholesterol crystals) in the vessel wall3. Platelet adhesion4. Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and foam cells5. Lipid accumulation within macrophages (foam cells), which release inflammatory cytokines

Response-to-injury hypothesis6. Smooth muscle cell recruitment due to factors released from activated platelets, macrophages, and vascular wall cells7. Smooth muscle cell proliferation and ECM production - Smooth Muscle Proliferation and Matrix Synthesis8. Formation of fatty streak9. Formation of lipid plaque/atheroma/atheromatous plaque

Types of Atherosclerotic Plaque Stable plaque and Unstable plaque Compared to stable atherosclerotic plaques,

unstable plaques that are vulnerable to rupture contain a larger necrotic lipid core rich in inflammatory cells and a thinner fibrous cap. Lp-PLA2 is secreted by inflammatory cells in the lesion or carried on LDL particles. Lp-PLA2 cleaves oxPC on the outer surface of oxLDL to generate lysoPC and oxFA. These two bioactive lipid products promote necrotic core expansion and thinning of the fibrous cap. oxFA, oxidized fatty acid.

Pathological ChangesThe advanced lesion of ATH is the most vulnerable to the following pathologic changes that have clinical significance:- Focal rupture, ulceration or lesion of the luminal surface of atheromatous plaques may result in exposure of highly thrombogenic substances that induce thrombus formation or discharge debris into bloodstream, producing microemboli - Hemorrhage into a plaque initiated by rupture of either the overlying fibrous cap or the thin walled capillaries that vascularize the plaque.- Aneurysmal dilation may result from ath induced pressure or ischemic atrophy of the underlying media with loss of elastic tissue causing weakness and potential rupture - Fatty streak composed of lipid laden foam cells

Aorta : fatty streaks

Aorta : mild, moderate, severe atherosclerosis

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