2015 Volume I Issue 1 Pages 46-51 Research Article Detection of Endothelin (ET-1 and ET-3) as a novel biomarker of cardiovascular stress in patients of liver cirrhosis with ascites Kalsoom Zaigham 1* , Iqra Fayyaz 1 , Khawar Ali Shahzad 1,2 , Muhammad Idrees Khan 3 , Muhammad Shahzad Iqbal 3 , Muhammad Ameen 1 , Ayisha Ayub 3 , Muhammad Zaigham Javed 1 1 Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore 54000, Pakistan 2 Department of Microbiology and Immunology, Southeast University, Nanjing 210009, China 3 Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54000, Pakistan Abstract Endothelin (ET) is an endothelial cell-derived peptide with greater vasoconstrictive potency involved in the control of systemic blood pressure (BP) and vascular tone. Dysfunctioning of ETs (endothelin-1 and endothelin-3) is considered a key risk factors for cardiovascular disease. The present study was aimed to find the correlation of endothelin and oxidative stress with cardiovascular stress. 50 Blood and ascitic fluid samples were collected from the patients of liver cirrhosis with ascites and 25 blood samples from normal individuals from General Hospital Lahore Pakistan. Endothelin-1 and endothelin-3 were quantified in serum and ascetic fluid by Real time PCR. Nitric oxide (NO), creatine kinase (CK), creatine kinase-MB (CK-MB), cholesterol, and C- reactive protein (CRP) were estimated as cardio vascular stress parameters and glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MAD) were estimated as biomarker of oxidative stress. ET-3 was quantified while ET-1 was not quantified due to very low concentration both in serum and ascitic fluid. Overall positive and highly significant (P<0.05) correlation of oxidative stress and cardiovascular stress with ET-3 was found. It was inferred that increase production of endothelin (ET-3) under oxidative stress generates cardiovascular stress in patients of liver cirrhosis with ascites. Keywords: Endothelin, superoxide dismutase (SOD), malondialdehyde (MAD), catalase (CAT), glutathione (GSH), antioxidative enzymes, cardiovascular disease. Received March 01, 2015; Revised April 05, 2015; Accepted April 12, 2015 * Correspondence: Kalsoom Zaigham, Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54000, Pakistan. Email: kalsimbb@yahoo.com, Contact +923117502868 To cite this manuscript Zaigham K, Fayyaz I, Shahzad KA, Khan MI, Iqbal MS, Ameen M, Ayub A, Javed MZ. Detection of Endothelin (ET-1 and ET-3) as a novel biomarker of cardiovascular stress in patients of liver cirrhosis with ascites. Biomed Lett 2015; 1(1):46-51. Introduction Endothelins are from the family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET- 2) and endothelin-3 (ET-3), each comprises 21 amino-acids [1]. The overall function of endothelin is to increase blood pressure and vascular tone. Endothelins are proteins that constrict blood vessels. They are normally kept in balance by other mechanisms; however, when they are over- expressed, they contribute to high blood pressure and heart disease. ET production is stimulated in a variety of different cell types under the influence of risk factors for cardio vascular stress and during development of CVD [2]. Endothelial dysfunction and the bioavailability of nitric oxide (NO) have been documented as one of many risk factors for cardiovascular disease [10]. Mechanisms that participate in the reduced vasodilatory responses in endothelial dysfunction include nitric oxide generation, oxidative stress, and reduced formation of hyperpolarizing factor [13]. Endothelin-1 and endothelin-3 has been implicated as an important factor in the development of vascular dysfunction and cardiovascular disease. In patients of liver cirrhosis with ascites there is induced production of oxidative stress with the production of endothelins. Portal hypertension is produced due to vasoconstriction. Splanchnic vascular and peripheral arterial vasodilation takes place which generates NO overproduction. In cirrhosis arteriolar vasodilation causes under filling systemic arterial vascular space. This event, through a decrease in effective blood volume leads to a drop in arterial pressure. Consequently baro- receptor activated renin-angiotensin aldosterone system (RAAS) occurs to restore normal blood homeostasis [5]. Splanchnic vasodilation causes increase lymph production that exceeds the lymph transportation system capacity and lead to lymph leakage in to the peritoneal cavity. RAAS produces vasoconstriction as a result cardiovascular stress is generated in patients of liver cirrhosis with ascites [12]. Keeping in view the role of endothelins in generating cardiovascular complications in liver cirrhosis, the present study was conducted to 46