Aterosklerozun Patofizyolojisi ve Risk Faktörleri

Dünyada ve ülkemizde ateroskleroz ve komplikasyonları en önde gelen ölüm nedenidir. ateroskleroz, tipik lezyonu ateroma plakları olan orta ve büyük çaplı arterlerin intima tabakalarını etkileyen bir hastalıktır. endotel disfonksiyonu aterosklerotik süreçteki temel mekanizmalardan biridir. klasik ve yeni belirlenen risk faktörleri endotelde vazodilatatör cevabın azalmasına yol açan kronik hasarlanma oluştururlar. Böylece endotelde oluşan vazokonstriksiyon, inflamatuvar hücrelerin birikimi, düz kas hücrelerinin migrasyonu, sitokin üretiminin artışı gibi olaylar aterosklerotik plak oluşumuna neden olurlar. endotel disfonksiyonu yalnız plak oluşumuna neden olan aterosklerotik sürecin ilk basamağı olmakla kalmaz, ayrıca oluşan plağın büyümesine, çatlamasına ve trombojenik olayların tetiklenmesine de neden olur. Hiperkolesterolemi; ateroskleroz patogenezinde rol oynayan en önemli faktördür. epidemiyoloji çalışmaları, pek çok genetik ve çevresel faktör arasında artmış serum kolesterol düzeylerinin, diğer bilinen risk faktörlerinin yokluğunda bile ateroskleroz gelişimine tek başına yeterli olduğunu göstermektedir. Bu çalışmada köpük hücrelerin oluşumunu sağlayarak ateroskleroz patogenezine katkısı bulunduğu düşünülen lipoproteinler incelenirken, bu fenomene katıldığı düşünülen pek çok parametrenin de ele alınarak değerlendirilmesi amaçlanmıştır.

atherosclerosis and its complications is the leading cause of death both in our country and in the world. atherosclerosis is a disease that affects the intima layers of medium and large arteries with its typical lesions “atherosclerotic plaques”. endothelial dysfunction is one of the basic mechanisms in the atherosclerotic process. Classic and newly identified risk factors leading to a decrease in the vasodilator response creates chronic injury. Thus, vasoconstriction composed in endothelium, accumulation of inflammatory cells, smooth muscle cell migration, cytokine production cause the increase of events such as the formation of atherosclerotic plaques. endothelial dysfunction is not only the first step of the atherosclerotic plaque formation process, but also cause triggering of atherogenic events cracking and the growth of plaque. The most important factor that plays a role in the pathogenesis of atherosclerosis is hypercholesterolemia. epidemiological studies indicate that along many genetic and environmental factors, increased serum cholesterol levels is enough alone for development of atherosclerosis in the absence of other known risk factors. In this study, lipoproteins that are considered to contribute formation of the pathogenesis of atherosclerosis by creating foam cells were examined and it is aimed to evaluate this phenomenon considering the many parameters joining it.

PDF

___

Faller Dv. endothelial cell responses to hypoxic stress. Clin exp Pharmacol Physiol 1999; 26: 74-84.

Carlson JT, rangemark C, Hedner Ja. attenuated endothelium dependent vascular relaxation in patients with sleep apnea. J Hypertens 1996; 14: 577-84.

Tetik Ş, ak k. kardiyovasküler hastalıklarda trombosit fonksiyon testleri: patofizyolojiden klinik yaklaşıma. Cumhuriyet Med J 2010; 32: 264-74.

Chen C, Halkos Me, Surowiec SM, Conklin BS, Lin PH, Lumsden aB. effects of homocysteine on smooth muscle cell proliferation in both cell culture and artery perfusion culture models. J Surg res 2000;88:26-33.

klein I, Ojamaa k. Thyroid hormone and the cardiovascular system. n engl J Med 2001;344:501-9.

Toft aD, Boon na. Thyroid disease and the heart. Heart 2000;84:455-60.

Yuvanç U, Çiçek D, Yeşilbursa D, karaağaç k, Şentürk T, Siğirli D, Jordan J. akut miyokard infarktüsünde ortalama trombosit hacminin bir yıllık mortalite ve revaskülarizasyon ihtiyacı üzerine etkisi. Mn-kardiyoloji Derg 2004;11:416-20.

Wallentin L, Lindahl B, Siegbahn a. Unstable angina and non ST-elevation MI. In: Cardiology, 1st ed. editors: Crawford MH, DiMarco JP, Paulus WJUSa. elsevier Science Limited. 2001.

Tetik Ş, ak k, Yardımcı kT. Trombosit fonksiyon testlerini etkileyen faktörler. Cumhuriyet Med J 2012; 34:123-7.

Sokolow M, Mcilory Me. Clinical cardiology, second edition. WB Saunders Com., new York. 1979, pp 124.

Helgeland a, Hjermann I, Leren P, enger S, Holme I. HDL cholesterol and antihypertensive drugs: the Oslo Study. Br Med J 1978;2:403.

Third report of the national Cholesterol education Program (nCeP) expert Panel on Detection, evaluation, and Treatment of High Blood Cholesterol in adults (adult Treatment Panel III) final report. Circulation 2002;106:3143-421.

roger vL, Go aS, Lloyd-Jones DM, Benjamin eJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford eS, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit Ja, Howard vJ, kissela BM, kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli a, Matchar DB, Moy CS, Mozaffarian D, Mussolino Me, nichol G, Paynter nP, Soliman eZ, Sorlie PD, Sotoodehnia n, Turan Tn, virani SS, Wong nD, Woo D, Turner MB; american Heart association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the american Heart association. Circulation 2012;125:188-97. erratum in Circulation 2012;125:e1001.

assmann, G. Dabetic Dyslipidaemia results From the Prospective Cardiovascular Münster Procam Study. Clinician 1990; 8 (l): 3-11.

Summary of revisions for the 2009 Clinical Practice recommendations. Diabetes Care 2009; 32 Suppl 1: S3-5. erratum in: Diabetes Care 2009; 32:754.

Bernstein rk. 2008 american Diabetes association Clinical Guidelines Comments. avaible from: http://www. diabetesbook.com/cms/articles/9-diabetes-in-control/5576richardk-bernstein-md-face-facn-fccws- Last access: 16th May 2011.

Shaw PX, Hörkkö S, Tsimikas S, Chang Mk, Palinski W, Silverman GJ, Chen PP, Witztum JL. Human–derived antioxidized LDL autoantibody blocks uptake of oxidized LDL by macrophages and localizes to atherosclerotic lesions in vivo. arterioscler Thromb vase Biol 2001; 21:1333-9.

Salonen JT, Ylä-Herttuala S, Yamamoto r, Butler S, korpela H, Salonen r, nyyssönen k, Palinski W, Witztum JL. autoantibody against oxidized LDL and progression of carotid atherosclerosis. Lancet 1992; 339: 883-7.

riesen W, noseda G. antibodies against lipoproteins in man. Occurence and significance. klin Wschr 1975;53:353-61.

Beaumont JL. Hyperlipidemia caused by anti-beta-lipoprotein autoantibodies. a new pathological entity. Cr acad Sci Hebd Seances acad Sci D 1965;261:4563-6.

Sakurai k, Sawamura T. Stress and vascular responses: endothelial Dysfunction via Lectin- Like Oxidized LowDensity Lipoprotein receptor-1: Close relationships with Oxidative Stress. J Pharmacol Sci 2003; 91:182-6.

Özlem k, Hülya Ya. Okside LDL reseptörü-1 (LOX-1) ve kardiyovasküler Hastalıklarla ilişkisi. Tıp araştırmaları Derg 2014;12:145-52.

Chen XP, DU GH. Lectin-like oxidized lowdensity lipoprotein receptor-1: protein, ligands, expression and pathophysiological significance. Chin Med J 2007;120:421-6.

kugiyama k, Sakamoto T, Misumi I, Sugiyama S, Ohgushi M, Ogawa H, Horiguchi M, Yasue H. Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells. Circ res 1993;73:33543.

kockx MM. apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects. arterioscler. Thromb vasc Biol 1998;18:1519-22.

Liao Jk, Shin WS, Lee WY, Clark SL. Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. J Biol Chem 1995;270:319-24.

Boulanger CM, Tanner FC, Bea ML, Hahn aW, Werner a, Luscher TF. Oxidized low density lipoproteins induce mrna expression and release of endothelin from human and porcine endothelium. Circ res 1992;70:1191-7.

Stiko-rahm a, Hultgardh-nilsson a, regnstrom J, Hamsten a, nilsson J. native and oxidized LDL enhances production of PDGF aa and the surface expression of PDGF receptors in cultured human smooth muscle cells. arterioscler Thromb 1992;12:1099-1109.

Doi H, kugiyama k, Oka H, Sugiyama S, Ogata n, koide SI, nakamura SI, Yasue H. remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation 2000;102:670-6.

Carr aC, McCall Mr, Frei B. Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. arterioscler Thromb vasc Biol 2000 Jul;20:1716-23.

Steinberg D. atherogenesis in perspective: Hypercholesterolemia and inflammation as partners in crime. nat Med 2002;8:1211-7.

Binder CJ, Chang Mk, Shaw PX, Miller YI, Hartvigsen k, Dewan a, Witztum JL. Innate and acquired immunity in atherogenesis. nat Med 2002;8:1218-26.

Yılmaz G. atorvastatin kullanan dislipidemi hastalarında tedavi öncesi ve 3 ay sonrası serum Paraoksonaz-1 ve okside LDL düzeyleri (Uzmanlık Tezi). Taksim eğitim ve araştırma Hastanesi, istanbul. 2008.

Seyfettin Ü. Hiperkolesterolemi ile Oluşabilecek Oksidatif Stresin ve Monosit CD36 reseptör ekspresyonunun ateroskleroz riski açısından Değerlendirilmesi (Uzmanlık Tezi). MÜ Tıp Fakültesi Biyokimya anabillim Dalı, istanbul. 2012.

kardiyoloji Miniatlas, 1. Baskı. anD danışmanlık, eğitim, yayıncılık ve organizasyon Ltd. Şti. 2003, pp 155-162.

Stary HC, Chandler aB, Dinsmore re, Fuster v, Glagov S, Insull W Jr, rosenfeld Me, Schwartz CJ, Wagner WD, Wissler rW. a definition of advanced types of atherosclerotic lesions and histological classification of atherosclerosis. a report from the Committee on vascular Lesions of the Council on arteriosclerosis ,american Heart association. Circulation 1995 ;92:1355-13.

Özdoğu H. inflamasyonda baş aktör endotel. Türkiye Hematoloji Derneği (6. ilk basamak kursu), ankara. 2007.

Harrison DG. endothelial function and oxidant stress. Clin Cardiol. 1997;20:11-17.

Cominacini L, rigoni a, Pasini aF, Garbin U, Davoli a, Campagnola M, Pastorino aM, Lo Cascio v, Sawamura T. The binding of oxidized low-density lipoprotein (ox-LDL) to oxLDL receptor-1 in endothelial cells reduces the intracellular concentration of nitric oxide through an increased production of superoxide. J Biol Chem 2001;276:13750–5.

Libby P, ridker PM, Maseri a. Inflammation and atherosclerosis. Circulation. 2002;105:1135–43.

Gauthier TW, Scalia r, Murohara T, Guo JP, Lefer aM. nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia. arterioscler Thromb vasc Biol 1995;15:1652–9.

Yalın TY, Mete k. endotel Disfonksiyonu. Pamukkale Tıp Derg 2011; 4:152-7.

akçakoyun M. koroner arter hastalığı olgularında koroner risk faktörleri ile endotel fonksiyonları arasındaki ilişki (Uzmanlık Tezi). koşuyolu kalp eğitim ve araştırma Hastanesi, istanbul. 2004.

vallance PJT, Webb DJ. vascular endothelium, its physiology and pathophysiology. CrC Press, 2003.

Halit Z. ateroskleroz patogenezi. Deneysel ve klinik Tıp Derg 2012; 29: 101-6.