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ATHEROSCLEROSIS

DEFINITION
Athere : Gruel, Skleros : hardness Atherosclerosis is a complex disease process that involves lipoprotein influx, lipoprotein modification, increased prooxidant stress, and inflammatory, angiogenic, and fibroproliferative responses intermingled with extracellular matrix and lipid accumulation resulting in the formation of an atherosclerotic plaque

NORMAL ARTERY

RISK FACTORS

Dyslipidemia and atherogenic lipoprotein modification Elevated LDL, VLDL, LP(a) LDL modification (oxidation, glycation) Reduced HDL Increased oxidant stress Hypertension, excess angiotensin II, diabetes, smoking Obesity and insulin resistance Estrogen deficiency Hyperhomocysteinemia Advancing age Genetic factors Infections? Lack of physical activity

ENDOTHELIAL DYSFUNCTION

ENDOTHELIAL DYSFUNCTION

ATHEROSCLEROSIS KEY-STEPS

FATTY STREAK

PLAQUE PROGRESSION

PLAQUE DISRUPTION

FATTY STREAK FORMATION

LIPOPROTEIN ENTRY AND MODIFICATION

LDL enter the injured endothelium and bind to proteoglycans and trapped in the subendothelium

FOAM CELL FORMATION

LEUKOCYTE RECRUITMENT
Depend on expression of leukocyte adhesion molecules (LAM) on the normally nonadherent endothelial luminal surface, and chemoattractant signals (e.g., monocytechemotactic protein 1 [MCP1], IL-8, IP-10) that direct diapedesis (passage of cells through the intact endothelium) into the subintimal space. Plaque LAMs and chemoattractant signals direct mainly monocytes to the forming lesion.

FOAM CELL FORMATION

The classic LDL receptor does not recognize chemically modified LDL. Rather, macrophages rely on a family of scavenger receptors that preferentially bind and internalize mLDL. Continued inflammation results in increased numbers of macrophages and lymphocytes, which both emigrate from the blood and multiply within the lesion. Activation of these cells leads to the release of proteolytic enzymes, cytokines, chemokines, and growth factors, which can induce further damage and eventually lead to focal necrosis. Necrosis and/or apoptosis of foam cells results in the formation of the necrotic lipid core in the plaque

PLAQUE PROGRESSION

PLAQUE PROGRESSION

STABLE ATHEROSCLEROTIC PLAQUE

UNSTABLE ATHEROSCLEROTIC PLAQUE

RUPTURED ATHEROSCLEROTIC PLAQUE

PLAQUE DISRUPTION
Plaque instability depend on: Protrusion plaque size The net deposition and distribution of the fibrous cap is an important determinant of overall plaque integrity

COMPLICATIONS
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Calcifi cation Rupture or ulceration of atherosclerotic Plaque Hemorrhage into the plaque owing to rupture of the fi brous cap or of the microvessels that form within the lesion. Embolization of fragments of disrupted atheroma to distal vascular sites. Weakening of the vessel wall Microvessel growth within plaques, providing a source for intraplaque hemorrhage and further leukocyte traffi cking.

CONCLUSION
Endothelial dysfunction is common in atherosclerosis and often manifests as a reduced vasodilator or enhanced vasoconstrictor phenotype, which contribute to luminal compromise Thrombosis resulting from plaque rupture or superficial erosion complicates atherosclerosis, often resulting in abrupt luminal occlusion with resultant acute ischemic syndromes

REFERENCES
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Badimon Jose, et al. Pathophysiology of Vulnerability Caused by Thrombogenic (Vulnerable) Blood. In: Asymptomatic Atherosclerosis : Pathophysiology Detection and Treatment. Humana Press Libby Peter, Strom B. Jordan. Atherosclerosis. In: Pathophysiology of Heart Disease Fifth Edition. Lippincott Williams & Wilkins. Philadelpia. 2011 Lyon C, George J. sarah. Pathogenesis of Atherosclerosis. In: Atherosclerosis Molecular and Cellular Mechanisms. Wiley Blackwell. WeinHeim. 2006 Shah K. Prediman. Pathogenesis of Atherosclerosis. In: Essential Cardiology Principles and Practice. Humana Press. New Jersey. 2005

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