Inflammatory and Apoptotic Markers in Ischemic Heart Disease Patients

Inflammatory and Apoptotic Markers in Ischemic Heart Disease Patients Ischemic heart disease is the most frequent cause of cardiovascular morbidity and mortality. It is developed on the basis of atherosclerosis which is today considered a chronic inflammatory disease. It is documented by an increase in inflammatory and immune biomarkers, such as C-reactive protein, fibrinogen, neopterin, leukocytes, lymphocytes and others, that are significantly changed in patients with unstable angina or acute myocardial infarction. CRP is mostly studied. Increased concentrations of CRP are associated with a series of risk factors. CRP may predict recurrent events and mortality independently of cardiac troponin levels, and it is also an independent predictor of a cardiovascular event after adjustment for traditional risk factors. Although CRP currently appears to be the most promising biological marker, there is still controversy regarding its use in clinical practice. Both necrotic and apoptotic cell death are documented during atherogenesis, however, limited data are available about apoptotic markers in ischemic heart disease patients. Increasing evidence supports the existence of apoptotic death initiated by ligation of membrane-bound death receptors or by release of cytochrome c from mitochondria, as well as their regulators in the heart. The studies of serum markers show that the apoptotic process is disregulated in ischemic heart disease patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is present in stable atherosclerotic lesions, is increased in vulnerable plaques, but its serum levels are reduced significantly in patients with unstable angina. Serum Fas concentrations are increased and FasL are decreased in subjects at high cardiovascular risk. The results of our study show significant changes in serum Fas, FasL, and Bcl-2 concentrations, and lymphocyte caspase-3 activity in different stages of ischemic heart disease. For now, there is evidence that statins are effective in the regulation of some apoptotic markers. The better understanding of the pathways of apoptosis and their regulation is promissing in yielding novel therapeutic targets for cardiovascular disease. Markeri Inflamacije i Apoptoze Kod Bolesnika sa Ishemijskom Bolešću Srca Ishemijska bolest srca je najčešći uzrok kardiovaskularnog morbiditeta i mortaliteta. Razvija se na terenu ateroskleroze koja se danas smatra hroničnom inflamatornom bolešću. Inflamacija je dokazana praćenjem inflamatornih i imunih biomarkera kao što su C-reaktivni protein (CRP), fibrinogen, neopterin, leukociti, limfociti i drugi koji se značajno menjaju kod bolesnika sa nestabilnom anginom pektoris ili akutnim infarktom miokarda. Najčešće ispitivan marker je CRP. Povećane koncentracije CRP su udružene sa brojnim faktorima rizika. Na osnovu vrednosti CRP mogu se predvideti rekurentni događaji i mortalitet nezavisno od vrednosti srčanog troponina, a takođe je nezavisan prediktor kardiovaskularnog događaja nakon korekcije tradicionalnih faktora rizika. Iako se CRP trenutno smatra biološkim markerom koji najviše obećava, još uvek postoje nedoumice u vezi sa njegovim korišćenjem u kliničkoj praksi. Mada je dokazano da se i nekroza i apoptoza dešavaju u toku aterogeneze, malo je dostupnih podataka koji se odnose na markere apoptoze kod bolesnika sa ishemijskom bolešću srca. Sve je više informacija koje ukazuju da se u srcu odvijaju apoptoza kao i njena regulacija, i da se apoptoza može inicirati preko membranskih receptora smrti, ali i oslobađanjem citohroma c iz mitohondrija. Ispitivanje serumskih markera je pokazalo da je proces apoptoze poremećen kod bolesnika sa ishemijskom bolešću srca. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) prisutan je u stabilnim aterosklerotskim lezijama, povećan u vulnerabilnim plakovima, dok su njegove serumske vrednosti značajno snižene kod bolesnika sa nestabilnom anginom. Koncentracija serumskog Fas je povećana, a FasL snižena kod osoba sa visokim rizikom. Rezultati naše studije su pokazali značajne promene koncentracija Fas, FasL i Bcl-2 u serumu, kao i aktivnost kaspaze-3 u limfocitima u različitim stadijumima ishemijske bolesti srca. Za sada postoje podaci o efektivnosti statina u regulaciji nekih markera apoptoze. Bolje razumevanje puteva apoptoze i njihove regulacije može omogućiti nov terapijski pristup kardiovaskularnim bolestima.