Adina Elena Stanciu1, Marcel Marian Stanciu2, Radu Gabriel Vatasescu3. 1. Institute of Oncology Bucharest, Department of Carcinogenesis and Molecular Biology, 252 Fundeni, 022338 Bucharest, Romania. Electronic address: adinaelenastanciu@yahoo.com. 2. University Politehnica of Bucharest, Electrical Engineering Faculty, 313 Splaiul Independentei, 060042 Bucharest, Romania. 3. Clinic Emergency Hospital Bucharest, Department of Cardiology, 8 Calea Floreasca, 014461 Bucharest, Romania.
Abstract
PURPOSE: Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines (IL-6, IL-1β, IL-8, TNF-α and IL-4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices. METHODS: We enrolled 32 subjects (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: All investigated biomarkers were significantly higher in CHF patients than in non-CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1β levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT-proBNP, CS IL-6 and CS IL-1β serum concentrations were inversely related to the echocardiographically determined left ventricular ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = -0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL-1β (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r = 0.43, P = 0.015), TNF-α (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002). CONCLUSIONS: CS sampling of NT-proBNP, CA 125 and pro-anti-inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation.
PURPOSE:Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines (IL-6, IL-1β, IL-8, TNF-α and IL-4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices. METHODS: We enrolled 32 subjects (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHFpatient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: All investigated biomarkers were significantly higher in CHFpatients than in non-CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1β levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT-proBNP, CS IL-6 and CS IL-1β serum concentrations were inversely related to the echocardiographically determined left ventricular ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = -0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL-1β (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r = 0.43, P = 0.015), TNF-α (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002). CONCLUSIONS: CS sampling of NT-proBNP, CA 125 and pro-anti-inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation.
Authors: Mihail Silviu Tudosie; Genica Caragea; Dragos Marian Popescu; Oana Avram; Dragos Serban; Catalin Gabriel Smarandache; Corneliu Tudor; Cristinel Dumitru Badiu; Bogdan Socea; Alexandru Dan Sabau; Meda Comandasu; Radu Spataru; Daniel Ovidiu Costea; Ciprian Tanasescu; Ana Maria Dascalu Journal: Exp Ther Med Date: 2021-07-13 Impact factor: 2.447
Authors: Kuldeep Dhama; Shyma K Latheef; Maryam Dadar; Hari Abdul Samad; Ashok Munjal; Rekha Khandia; Kumaragurubaran Karthik; Ruchi Tiwari; Mohd Iqbal Yatoo; Prakash Bhatt; Sandip Chakraborty; Karam Pal Singh; Hafiz M N Iqbal; Wanpen Chaicumpa; Sunil Kumar Joshi Journal: Front Mol Biosci Date: 2019-10-18
Authors: Patrícia Lourenço; Filipe M Cunha; Catarina Elias; Catarina Fernandes; Isaac Barroso; João T Guimarães; Paulo Bettencourt Journal: ESC Heart Fail Date: 2022-01-05
Authors: Weronika Bulska-Będkowska; Elżbieta Chełmecka; Aleksander J Owczarek; Katarzyna Mizia-Stec; Andrzej Witek; Aleksandra Szybalska; Tomasz Grodzicki; Magdalena Olszanecka-Glinianowicz; Jerzy Chudek Journal: J Clin Med Date: 2019-05-03 Impact factor: 4.241
Authors: C Shi; H H van der Wal; H H W Silljé; M M Dokter; F van den Berg; L Huizinga; M Vriesema; J Post; S D Anker; J G Cleland; L L Ng; N J Samani; K Dickstein; F Zannad; C C Lang; P L van Haelst; J A Gietema; M Metra; P Ameri; M Canepa; D J van Veldhuisen; A A Voors; R A de Boer Journal: J Intern Med Date: 2020-05-05 Impact factor: 8.989