Pathogenesis of Atherosclerosis a Review
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2016 Vol.2No.3:22 DOI 1O.)11 6l /2 41 1-)99X.1OOO}1 Pathogenesis of Atherosclerosis A Review Maria Aziz ln this review, we would discuss the chief pathways involved in the pathophysiology of atherosclerosis. We would also highlight the end terminal events of this sequel with due consideration to risk factors, clinical features, diagnosis and Director, Pri-Med Care, Lewisville, Texas treatment. The aim of the review is to get into the fine details of all possible 75067, U5A. causes and pathophysiologic mechanisms responsible for atherosclerosis so that new treatment modalities can emerge and reduce the morbidity and mortality [email protected] associated with atherosclerosis. l= ref.9723656942 August 05, 2016; August 22, 2OL6; August 29,2016 Aziz M, Yadav KS. Pathogenesis of Introduction Atherosclerosis. Med Clin Rev. 2016,2.3. Atherosclerosis has been derived from a Greek word, Athero meaning gruel [1]. Marchand introduced the term Discussion "atherosclerosis" describjng the assosciation of fatty degeneration and vessel stiffening [2]. lt's the patchy intramural thickening of We would discuss the chief pathways involved in the the subintima. The earliest lesion is the fatty streak. Fatty streak pathophysiology of atherosclerosis. We would also highlight the end events of this sequel with due consideration to risk evolve to fibrous plaque and unstable plaque are responsible for terminal clinical events. factors, clinical features, diagnosis and treatment. Atherosclerosis is marked by atheromas, patchy intimal Pathophysiology plaques. Most common location is lumen of medium sized and Atherosclerosis is a chronic inflammatory disease. Atherosclerosis plaque -namely large arteries. The has cellular component of begins with fatty streak which is a accumulation of lipid laden inflammatory cells, smooth muscle cells, a fibrous component of foam cells in the intimal layer of the artery [4]. Lipid retention -connective tissue and a fat component of lipids. Prominent risk is the first step in the pathogenesis of atherosclerosis which is factors of consideration are Hypertension, Diabetes, Dyslipidemia, followed by chronic inflammation at susceptible sites in the walls obesity, sedentary life style, Family history, smoking. Intraplaque of the major arteries lead to fatty streaks, which then progress to (Table 1) rupture, bleeding, thrombosis and stenosis cause symptoms. fibroatheromas which are fibrous in nature [5,6]. Diagnosis is clinical and definitive diagnosis is made through Atherosclerosis is a continuous progressive development. Fatty lmaging tests. Management plan includes behavior modifi€ations streak develop at 11-12 years and fibrous plaques at 15 30 years (Figure (Physical activity with low caloric diet, rich in fiber component) 1, depicts the conversion of Fatty Streak to Fibrous Plaques) [7] and they develop at the same anatomic sites as the and main class of drugs used in treatment are antiplatelet drugs fatty streaks making it more evident that fibrous plaques arise and antiatherogenic drugs. from fatty streak. Pathologic intimal thickening leads to fatty plaques, finally It is the leading cause of morbidity and mortality in the US and streak, leads to fibrous cap atheromas, lead to leading to sudden cardiac death western world. ln the current era cardiovascular disease (CVD) [8,9]. remains the MCC of death all over the world. In 2008, 17 million Fatty streaks evolve to atherosclerotic plaques which is composed deaths were recorded from CVD. More than 3 million of these of three components namely of inflammatory cells, smooth muscle a fibrous component of-connective tissue and a Fat deaths occurred in people below the age of 6o and could have cells, component of lipids [10]. largely been prevented [3]. There are growing inequalities in the occurrence and outcome of CVD between countries and social Endothelial Injury plays the inciting role. Turbulent blood flow classes. leads to endothelial dysfunction, it inhibits production of No, o Under License ofCreative Commons Attribution 3-O License I http//medical-clinical-reviews.imedpub.com/archive-php 2016 Vol.2 No. 3 :22 Table 1 Stages of Atherosclerosis: Modified AHA consensus classification based on morphologic descriptions. Nonatherosclero$c intimal lesions Normal accumulation of smooth muscle cells (SMCs) in the intima in the absence of lipid Intimalthickening Absent or macrophage foam cells. Superficial accumulation of foam cells without a necrotic core or fibrous cap; based on lntimalxanthoma animal and human data, such lesions usually regress. Progressive athercsclerotic lesions Pathologic intimal thickening sMC rich plaque with proteoglycan matrix and focal accumulation of extracellular lipid Absent Early necrosis: focal macrophage infiltration into areas of lipid pools with an overlying Fibrous cap atheroma fibrous cap Late necrosis: loss of matrix and extensive cellular debris with an overlying fibrous cap. A thin, fibrous cap (< 65 Bm) infiltrat€d by macrophages and lymphocytes with rare or Thin cap fibroatheroma absence oJ sMcs and a relativelv large underlying necrotic corej intraplaque hemorrhage/ Absent - fibrin mav be present. Lesions with acute thrombi Fibroatheroma with fibrous cap disruption; the luminalthrombus communicates with the occlusive or Plaque rupture underlying necrotic core nonocclu5rve Plaque composition, as abovej no communacation ofthe thrombus with the necrotic core; Plaque erosion Usually nonocclusive can occur on a plaque substrate of pathologic intimal thickening or fibroatheroma Eruptive (shedding) of calcified nodules with an underlying fibrocalcific plaque with calcifed nodule Usually nonocclusive minimal or absence of necrosis Lesions with healed thrombi Fibrotic (without calcifi cation) Collagen-rich plaque with 5ignificant luminal stenosis; lesions may contain large areas of calcification with few inflammatory cells and minimal or absence of necrosis; these Absent Fibrocalcific {+/- necrotic core) lesions may represent healed erosions or ruptures Lesion reference to AHA types V and Vl was discarded, because it failed to account for the 3 different fiorphologies {rupture, erosion, and calcified nodule)that give rise to acute coronary thrombosis- of clinically silent ruptures leads to multiple layer of healed tissue Fatty Streak Fibrous Plaque and the end result is sudden cardiac death. calcium deposits (15 yeaf) (11 - 12 year) - 30 as small aggregates convert later to large nodules in the wall. Erosion of endothelium leads to thrombosis. Increase plaque mass causes stenosis and finally leading to lethal ischemia [12]. Figure 1 Conversion of fatty streak to Fibrous plaques. There are two types of plaques stable and unstable I131. stable plaques regress or are static or they grow slowly. Unstables a potent vasodilator and stimulates production of adhesion plaques are complicated by erosion, fissure, rupture and cause molecules which attract inflammatorv cells, Other risk factors also stenosis. thrombosis, infarction. Most clinical events result from contribute to this step. The net result is Monocytes and T cells complications of unstable plaque, hence plaque stabilization can bind to the endothelial cells and migrate to the subendothelial reduce morbidity and mortality associated with atherosclerosis. space. Lipids in the blood, LDL, VLDL bind to endothelial cells and Plaque is ruptured by enzymes secreted by activated macrophages oxidize in the subendothelial space. Monocytes in subendothelial in the plaque. Once plaque ruptures, plaque contents get exposed space engulf oxidized LDL and transform to foam cells. Thls mark to circulating blood and the end result is thrombosis [14]. The the first stage i.e-, fatty streak. Macrophages further elaborate resultant thrombosis may change plaque shape, occlude lumen proinflammatory cytokines which recruit smooth muscle cells. of blood vessel, may embolise or the plaque contents may There is smooth muscle cell replication and increase in dense embolise. Low risk plaoues are more fibrous in content and 100% blockade while unstable extracellular matrix. End result lesion is a subendothelial fibrous have low lipids and do not cause plaques have thick lipid core and thin fibrous cap narrow lumen plaque composed of lipid core surrounded by smooth muscle <50% and tend to rupture unpredictably [15]. cells and connective tissue fibers (Figures 2 and 3) [11]. The end result of the stenosis caused by the plaques are There is sequential involvement of arterial layers, intima, then the Terminal Events-Acute Coronary Syndrome, Myocardial media and finally adventitia. Arterial wall lesions have a central Infarction, Fatal Arrhythmias, sudden cardiac death (Figures 4 cholesterol rich lipid core surrounded by inflammatory response. and 5 depict the terminal events that arise due to stenosis due Everv lesion has lipid accumulation and inflammation. Plaque to plaques) [16]. distorts media/adventitia, increases caliber of arterial lumen and decreases its size simultaneously. New Vasa Vasorum invade diseased intima, cause hemorrhage wilhin arterial wall, leading to Age, Family history, Male sex, smoking, Diabetes mellitus, intramural hemorrhage and increased fibrous tissue. Rupture of hypertension, alcohol, Chlamydia infection, Hyper thin fibrous caps leads to thrombosis and healing. cyclic healing homocysteinemia, Obesity, Sedentary lifestyle [17]. hft p://mediaal-clinical-reviews.imedpub.com/archive.php 2016. Vol.2 No.3:22 Lipid Retention Traditional Rlso Faciors Oxidation Modification /", // ^ |. t+ype{ension