Athero-heme and vascular calcification  Page description

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Details of project

 
Identifier
112333
Type K
Principal investigator Balla, József
Title in Hungarian Atero-hem és vaszkuláris kalcifikáció
Title in English Athero-heme and vascular calcification
Keywords in Hungarian hem, vas, hemoglobin, oxidáció, ferritin, hemoxigenáz, simaizomsejt, atherosclerosis, media sclerosis, calciphylaxis
Keywords in English heme, iron, hemoglobin, oxidation, ferritin, heme oxygenase, smooth muscle cells, atherosclerosis, media sclerosis, calciphylaxis
Discipline
Public health, health services, environmental and occupational medicine, epidemiology, medical ethics (Council of Medical and Biological Sciences)60 %
Ortelius classification: Nephrology
Cardiovascular system (Council of Medical and Biological Sciences)20 %
Cardiovascular system (Council of Medical and Biological Sciences)20 %
Ortelius classification: Cardiovascular system
Panel Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent Institute of Internal Medicine (University of Debrecen)
Participants Balla, György
Balláné Oros, Melinda
Balogh, Enikő
Gáll, Tamás
Gyetvai, Ágnes
Hendrik, Zoltán
Jeney, Viktória
Nyitrai, Mónika
Posta, Niké
Potor, László
Sikura, Katalin Éva
Starting date 2015-01-01
Closing date 2018-12-31
Funding (in million HUF) 43.432
FTE (full time equivalent) 25.85
state running project





 

Final report

 
Results in Hungarian
Laboratóriumunk korábban leírta, hogy az érelmeszesedéses plakk területén hem-stressz észlelhető, amit elsősorban a vörösvértest eredetű hemoglobin oxidációja okoz. A jelenlegi kutatási időszakban vizsgálataink a hem sorsának tanulmányozására irányult. Felismertük, hogy az érelmeszesedés területén a hemoglobin oxidációja gátlás alatt áll, amit a cisztation-gamma-liáz (CSE) és cisztation-béta-szintáz (CBS) által generált kénhidrogén gáz biztosít. Kimutattuk, hogy a kénhidrogén gátolja a hemoglobin és a hem oxidációját. CSE/CBS/H2S hiányállapotban szabad hem jelenik meg az erek falában, melynek eredménye az endoplazmatikus retikulum stressz (ER stressz) kialakulása. Az ER stressz létrejöttét képes gátolni, a lokálisan szintetizált alfa-1-mikroglobulin és a máj által termelt hemopexin. Exogén kénhidrogén forrás biztosítása donor molekulák alkalmazásával visszaállítható a H2S élettani szintje, és ezzel az erek kóros átalakulása sem következik be. A hem-stressz megjelenésével egyidőben az erek és a szívbillentyűk sejtjeiben (vaszkuláris simaizom sejtek, valvuláris interstíciális sejtek, őssejtek) adaptációs mechanizmusok fejlődnek ki, melynek molekuláris letéteményesei a H-ferritin és a CSE/CBS rendszer. A 3H-1, 2-ditiol-3-tion (D3T) emelve a H-ferritin szintjét gátolja a vaszkuláris mineralizációt. A CSE/CBS rendszer a H2S szintjének emelésén keresztül szintén anti-kalcifikációs tulajdonsággal rendelkezik.
Results in English
Since our laboratory previously revealed that in the progression of atherosclerosis exposure of arteries to heme derived from hemoglobin occurs we examined their fate within the lesion. We revealed that hydrogen sulfide gas within the vascular wall generated by Cystathione-gamma lyase (CSE) and Cystathionine beta-synthase (CBS) enzymes represents an atheroprotective pathway for removing or limiting the formation of oxidized hemoglobin, heme and lipid derivatives. Failure of CSE-CBS/H2S system allows heme to trigger Endoplasmic Reticulum stress in vascular cells, unless alfa-1-microglobulin and hemopexin hamper such an insult. Employing donors (NaSH, Na2S, GYY4137, AP67, AP72) as exogenous hydrogen source to enhance its level or for supplementation inhibits remodeling of vessels. We demonstrated that induction of H-ferritin represents an adaptive cellular response to heme exposure by the vessels (vascular smooth muscle cells, valvular interstitial cells, stem cells) that inhibits vascular mineralization and osteoblastic trans-differentiation of resident and stem cells. We explored that utilization of 3H-1, 2-dithiole-3-thione (D3T) to induce ferritin expression prove a novel therapeutic potential in valvular and vascular mineralization. CSE-CBS/H2S system was explored to also exhibit a direct anti-calcification function providing a novel therapeutic approach to prevent hardening of vessels and valves
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=112333
Decision
Yes





 

List of publications

 
KE Sikura, T Szerafin, A Zarjou, A Agarwal, G Alvarado, Z Hendrik, Gy Balla, J Balla: Targeting H-ferritin to mitigate valvular mineralization, 9th International Conference on Heme Oxygenases Prague 2016-BOOK OF ABSTRACT, 2016, 2016
Sumegi A, Nagy P, Fiatal Sz, Adany R, Olvaszto S, Balla Gy, Balla J: GT-repeat Polymorphism in the Heme Oxygenase-1 Gene Promoter Shows Association with Severe Carotid Atherosclerosis, 9th International Conference on Heme Oxygenases Prague 2016-BOOK OF ABSTRACT, 2016, 2016
Jakab Á, Emri T, Sipos L, Kiss Á, Kovács R, Dombrádi V, Kemény-Beke Á, Balla J, Majoros L, Pócsi I.: Betamethasone augments the antifungal effect of menadione--towards a novel anti-Candida albicans combination therapy., J Basic Microbiol., 2015
Bolisetty S, Zarjou A, Hull TD, Traylor AM, Perianayagam A, Joseph R, Kamal AI, Arosio P, Soares MP, Jeney V, Balla J, George JF, Agarwal A.: Macrophage and epithelial cell H-ferritin expression regulates renal inflammation., Kidney Int., 2015
Balogh E, Tolnai E, Nagy B Jr, Nagy B, Balla G, Balla J, Jeney V.: Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin., Biochim Biophys Acta, 2016
Becs G, Hudák R, Fejes Z, Debreceni IB, Bhattoa HP, Balla J, Kappelmayer J.: Haemodiafiltration elicits less platelet activation compared to haemodialysis., BMC Nephrol., 2016
Varga VE, Lőrincz H, Zsíros N, Fülöp P, Seres I, Paragh G, Balla J, Harangi M.: mpact of selective LDL apheresis on serum chemerin levels in patients with hypercholesterolemia., Lipids Health Dis., 2016
Balogh E, Nagy B Jr, Gyetvai Á, Bene Z, Hendrik Z, Jeney V, Nagy P, Papp Á, Balla J, Balla G, Kappelmayer J, Nagy B.: Impaired Immunosuppressive Effect of Bronchoalveolar Mesenchymal Stem Cells in Hypersensitivity Pneumonitis: Preliminary Findings., Cytometry B Clin Cytom, 2018
Greil J, Verga-Falzacappa MV, Echner NE, Behnisch W, Bandapalli OR, Pechanska P, Immenschuh S, Vijayan V, Balla J, Tsukahara H, Schneider M, Janka G, Claus M, Longerich T, Muckenthaler MU, Kulozik AE.: Mutating heme oxygenase-1 into a peroxidase causes a defect in bilirubin synthesis associated with microcytic anemia and severe hyperinflammation., Haematologica., 2016
Jakab Á, Antal K, Emri T, Boczonádi I, Imre A, Gebri E, Majoros L, Pfliegler WP, Szarka M, Balla G, Balla J, Pócsi I.: Effects of hemin, CO2, and pH on the branching of Candida albicans filamentous forms., Acta Microbiol Immunol Hung, 2016
Gáll T, Lehoczki G, Gyémánt G, Emri T, Szigeti ZM, Balla G, Balla J, Pócsi I.: Optimization of desferrioxamine E production by Streptomyces parvulus., Acta Microbiol Immunol Hung., 2016
Berkes A, Szikszay E, Kappelmayer J, Kerényi A, Szabó T, Ujhelyi L, Bari K, Balla G, Balla J.: Use of Hemadsorption in a Case of Pediatric Toxic Shock Syndrome., Case Rep Crit Care., 2017
Szigeti ZM, Talas L, Palicz Z, Szentesi P, Hargitai Z, Csernoch L, Balla J, Pocsi I, Banfalvi G, Szeman-Nagy G.: Murine model to follow hyphal development in invasive pulmonary aspergillosis., Appl Microbiol Biotechnol., 2018
Csongrádi A, Enyedi A, Takács I, Végh T, Mányiné IS, Pólik Z, Altorjay IT, Balla J, Balla G, Édes I, Kappelmayer J, Tóth A, Papp Z, Fagyas M.: Optimized angiotensin-converting enzyme activity assay for the accurate diagnosis of sarcoidosis., Clin Chem Lab Med., 2018
Potor L, Nagy P, Méhes G, Hendrik Z, Jeney V, Pethő D, Vasas A, Pálinkás Z, Balogh E, Gyetvai Á, Whiteman M, Torregrossa R, Wood ME, Olvasztó S, Nagy P, Balla G, Balla J.: Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction in Atherosclerotic Lesion, Oxid Med Cell Longev., 2018
Diószegi Á, Tarr T, Nagy-Vincze M, Nánásy-Vass M, Veisz R, Bidiga L, Dezső B, Balla J, Szodoray P, Szekanecz Z, Soltész P.: Microthrombotic renal involvement in an SLE patient with concomitant catastrophic antiphospholipid syndrome: the beneficial effect of rituximab treatment., Lupus, 2018
Csepanyi E, Czompa A, Szabados-Furjesi P, Lekli I, Balla J, Balla G, Tosaki A, Bak I.: The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1., Int J Mol Sci, 2018
Fülöp T, Tapolyai MB, Zsom L, Molnar MZ, Abdul Salim S, Újhelyi L, Becs G, Balla J, Hamrahian M.: Successful Practice Transitioning Between Hemodialysis and Hemodiafiltration in Outpatient Units: Ten Key Issues for Physicians to Remember., Artif Organs, 2018
Fejes Z, Czimmerer Z, Szük T, Póliska S, Horváth A, Balogh E, Jeney V, Váradi J, Fenyvesi F, Balla G, Édes I, Balla J, Kappelmayer J, Nagy B Jr.: Endothelial cell activation is attenuated by everolimus via transcriptional and post-transcriptional regulatory mechanisms after drug-eluting coronary stenting., PLoS One, 2018
Bereczki D Jr, Balla J, Bereczki D.: Heme Oxygenase-1: Clinical Relevance in Ischemic Stroke., Curr Pharm Des, 2018
Varga VE, Lőrincz H, Szentpéteri A, Juhász L, Seres I, Paragh G Jr, Balla J, Paragh G, Harangi M.: Changes in serum afamin and vitamin E levels after selective LDL apheresis., J Clin Apher, 2018
Priksz D, Bombicz M, Varga B, Kurucz A, Gesztelyi R, Balla J, Toth A, Papp Z, Szilvassy Z, Juhasz B.: Upregulation of Myocardial and Vascular Phosphodiesterase 9A in A Model of Atherosclerotic Cardiovascular Disease., Int J Mol Sci., 2018
Gáll T, Pethő D, Nagy A, Hendrik Z, Méhes G, Potor L, Gram M, Åkerström B, Smith A, Nagy P, Balla G, Balla J.: Heme Induces Endoplasmic Reticulum Stress (HIER Stress) in Human Aortic Smooth Muscle Cells., Front Physiol, 2018
Sikura K, Potor L, Szerafin T, Zarjou A, Agarwal A, Arosio A, Poli M, Hendrik Z, Méhes G, Oros M, Posta N, Balla G, Balla J: POTENTIAL ROLE OF H-FERRITIN IN MITIGATING VALVULAR MINERALIZATION, Arteriosclerosis, Thrombosis, and Vascular Biology, 2019
Becs G, Zarjou A, Agarwal A, Kovács KÉ, Becs Á, Nyitrai M, Balogh E, Bányai E, Eaton JW, Arosio P, Poli M, Jeney V, Balla J, Balla G: Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells, J Cell Mol Med, 2015
Alvarado G, Jeney V, Tóth A, Csősz É, Kalló G, Huynh AT, Hajnal C, Kalász J, Pásztor ET, Édes I, Gram M, Akerström B, Smith A, Eaton JW, Balla G, Papp Z, Balla J: Heme-induced contractile dysfunction in Human cardiomyocytes caused by oxidant damage to thick filament proteins, Free Radic Biol Med, 2015
Alvarado G, Toth A, Papp Z and Balla J: Heme induced contractile dysfunction in human cardiomyocytes by myofilament protein oxidation, 9th International Conference on Heme Oxygenases Prague 2016-BOOK OF ABSTRACT, 2016
Tolnai E, Balogh E, Pataki I, Nagy A, Katona E, Balla J, Balla G, Jeney V: Ferryl hemoglobin triggers inflammatory response upon intraventricular hemorrhage in premature infants, 9th International Conference on Heme Oxygenases Prague 2016-BOOK OF ABSTRACT, 2016, 2016





 

Events of the project

 
2015-04-07 09:00:12
Résztvevők változása




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