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01-03-2020 | Myocardial Infarction | Original Article

Increased inducible nitric oxide synthase (iNOS) expression in human myocardial infarction

Authors: Verena Wilmes, Stefanie Scheiper, Winta Roehr, Constanze Niess, Stefan Kippenberger, Katja Steinhorst, Marcel A. Verhoff, Silke Kauferstein

Published in: International Journal of Legal Medicine | Issue 2/2020

Abstract

Increased inducible nitric oxide synthase (iNOS) expression has been reported in heart failure, cardiomyopathies, and arteriosclerosis. iNOS is expressed in the heart upon inflammatory stimuli and produces excessive amounts of nitric oxide (NO). The overproduction of NO is cytotoxic and involved in cardiovascular diseases. Furthermore, iNOS produces superoxide anion which proceeds with NO to the harmful oxidant peroxynitrite, causing oxidative stress in the heart. The aim of the study was to gain new insights into the role of iNOS in human myocardial infarction (MI) and its contribution to oxidative stress in the heart. Furthermore, we investigated the unaffected myocardium of the infarction hearts, to study if iNOS expression is increased, probably as an indicator for oxidative stress. Our results show a significant increase (p = 0.013) of the iNOS expression in the affected regions of MI hearts (n = 9) in comparison with healthy control hearts (n = 4). In the unaffected regions of MI hearts, an increase in the iNOS expression in some samples was found as well. Our study demonstrated the direct detection of iNOS mRNA in human myocardial tissue. The balance between beneficial and deleterious effects of iNOS may be particularly influenced by the presence or absence of concurrent oxidative stress.

Lind M, Hayes A, Caprnda M, Petrovic D, Rodrigo L, Kruzliak P, Zulli A (2017) Inducible nitric oxide synthase: good or bad? Biomed Pharmacother 93:370–375CrossRef

Caimi G, Montana M, Calandrino V, Caruso M, Carollo C, Catania A, Lo Presti R (2008) Nitric oxide metabolites (nitrite and nitrate) in young patients with recent acute myocardial infarction. Clin Hemorheol Microcirc 40(2):157–163CrossRef

Searles CD (2002) The nitric oxide pathway and oxidative stress in heart failure. Congest Heart Fail 8(3):142–155CrossRef

Melillo G (1995) A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med 182(6):1683–1693CrossRef

Soskić SS, Dobutović BD, Sudar EM, Obradović MM, Nikolić DM, Djordjevic JD, Radak DJ, Mikhailidis DP, Isenović ER (2011) Regulation of inducible nitric oxide synthase (iNOS) and its potential role in insulin resistance, diabetes and heart failure. Open Cardiovasc Med J 5:153–163CrossRef

Brady AJ, Warren JB, Poole-Wilson PA, Williams TJ, Harding SE (1993) Nitric oxide attenuates cardiac myocyte contraction. Am J Phys 265(1 Pt 2):H176–H182

Li H-M, Liu L, Mei X, Chen H, Liu Z, Zhao X (2014) Overexpression of inducible nitric oxide synthase impairs the survival of bone marrow stem cells transplanted into rat infarcted myocardium. Life Sci 106(1–2):50–57CrossRef

Feng Q, Lu X, Jones DL, Shen J, Arnold JM (2001) Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice. Circulation 104(6):700–704CrossRef

Zhang P, Xu X, Hu X, van Deel ED, Zhu G, Chen Y (2007) Inducible nitric oxide synthase deficiency protects the heart from systolic overload-induced ventricular hypertrophy and congestive heart failure. Circ Res 100(7):1089–1098CrossRef

10.

Costa S, Reina-Couto M, Albino-Teixeira A, Sousa T (2016) Statins and oxidative stress in chronic heart failure. Rev Port Cardiol (Engl Ed) 35(1):41–57CrossRef

11.

Bailey A, Pope TW, Moore SA, Campbell CL (2007) The tragedy of TRIUMPH for nitric oxide synthesis inhibition in cardiogenic shock. Am J Cardiovasc Drugs 7(5):337–345CrossRef

12.

Huang H, Koelle P, Fendler M, Schröttle A, Czihal M, Hoffmann U, Conrad M, Kuhlencordt PJ (2014) Induction of inducible nitric oxide synthase (iNOS) expression by oxLDL inhibits macrophage derived foam cell migration. Atherosclerosis 235(1):213–222CrossRef

13.

Gori T, Münzel T (2011) Oxidative stress and endothelial dysfunction: therapeutic implications. Ann Med 43(4):259–272CrossRef

14.

Jones DP (2008) Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295(4):C849–C868CrossRef

15.

Münzel T, Gori T, Bruno RM, Taddei S (2010) Is oxidative stress a therapeutic target in cardiovascular disease? Eur Heart J 31(22):2741–2748CrossRef

16.

Gosslau A, Rensing L (2002) Oxidativer Stress, altersabhängige Zellschädigungen und antioxidative Mechanismen. Z Gerontol Geriatr 35(2):139–150CrossRef

17.

Ho E, Karimi Galougahi K, Liu C-C, Bhindi R, Figtree GA (2013) Biological markers of oxidative stress: applications to cardiovascular research and practice. Redox Biol 1:483–491CrossRef

18.

Paslawska U, Kiczak L, Bania J, Paslawski R, Janiszewski A, Dzięgiel P, Zacharski M, Tomaszek A, Michlik K (2016) Inducible NO synthase is constitutively expressed in porcine myocardium and its level decreases along with tachycardia-induced heart failure. Cardiovasc Pathol 25(1):3–11CrossRef

19.

Kunsch C, Medford RM (1999) Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 85(8):753–766CrossRef

20.

Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109(109 Suppl):S81–S96CrossRef

21.

Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115(3):500–508CrossRef

22.

Prabhu SD (2004) Nitric oxide protects against pathological ventricular remodeling: reconsideration of the role of NO in the failing heart. Circ Res 94(9):1155–1157CrossRef

23.

Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87(1):315–424CrossRef

24.

Koppelkamm A, Vennemann B, Fracasso T, Lutz-Bonengel S, Schmidt U, Heinrich M (2010) Validation of adequate endogenous reference genes for the normalisation of qPCR gene expression data in human post mortem tissue. Int J Legal Med 124(5):371–380CrossRef

25.

Pilbrow AP, Ellmers LJ, Black MA, Moravec CS, Sweet WE, Troughton RW, Richards AM, Frampton CM, Cameron VA (2008) Genomic selection of reference genes for real-time PCR in human myocardium. BMC Med Genet 1:64

26.

Hellemans J, Mortier G, de PA, Speleman F, Vandesompele J (2007) qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8(2):R19CrossRef

27.

Koppelkamm A, Vennemann B, Lutz-Bonengel S, Fracasso T, Vennemann M (2011) RNA integrity in post-mortem samples: influencing parameters and implications on RT-qPCR assays. Int J Legal Med 125(4):573–580CrossRef

28.

Pierini D, Bryan NS (2015) Nitric oxide availability as a marker of oxidative stress. Methods Mol Biol 1208:63–71CrossRef

29.

Tokmak A, Yıldırım G, Sarıkaya E, Çınar M, Boğdaycıoğlu N, Yılmaz FM, Yılmaz N (2015) Increased oxidative stress markers may be a promising indicator of risk for primary ovarian insufficiency: a cross-sectional case control study. Rev Bras Ginecol Obstet 37(9):411–416PubMed

30.

Menchén LA, Colón AL, Moro MA, Leza JC, Lizasoain I, Menchén P, Alvarez E, Lorenzo P (2001) N-(3-(aminomethyl)benzyl)acetamidine, an inducible nitric oxide synthase inhibitor, decreases colonic inflammation induced by trinitrobenzene sulphonic acid in rats. Life Sci 69(4):479–491CrossRef

Title: Increased inducible nitric oxide synthase (iNOS) expression in human myocardial infarction
Authors: Verena Wilmes
Stefanie Scheiper
Winta Roehr
Constanze Niess
Stefan Kippenberger
Katja Steinhorst
Marcel A. Verhoff
Silke Kauferstein
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keyword: Myocardial Infarction
Published in: International Journal of Legal Medicine / Issue 2/2020
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-019-02051-y

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Increased inducible nitric oxide synthase (iNOS) expression in human myocardial infarction

Abstract

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Abstract

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