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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

The Role of NAD+ in Myocardial Ischemia-induced Heart Failure in Sprague-Dawley Rats and Beagles

Author(s): Zuowei Pei, Chenguang Yang, Ying Guo, Min Dong and Fang Wang*

Volume 25, Issue 17, 2024

Published on: 13 February, 2024

Page: [2300 - 2311] Pages: 12

DOI: 10.2174/0113892010275059240103054554

Price: $65

Abstract

Introduction: Nicotinamide adenine dinucleotide (NAD+) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD+ may be cardioprotective. However, whether the protective effect exerted by NAD+ in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week, following which the animals were treated for 4 weeks with low, medium, and high doses of NAD+ and LCZ696.

Method: Cardiac function, hemodynamics, and biomarkers were evaluated during the treatment period. Heart weight, myocardial fibrosis, and MI rate were measured eventually.

Result: Compared with the HF groups, groups treated with LCZ696 and different doses of NAD+ showed increased ejection fractions, fractional shortening, cardiac output, and stroke volume and decreased end-systolic volume, end-systolic dimension, creatine kinase, and lactic dehydrogenase. LV blood pressure was lower in the HF group than in the control group, but this decrease was significantly greater in the medium and high NAD+ dose groups.

Conclusion: The ratios of heart weight indexes, fibrotic areas, and MI rates in the CZ696 and medium and high NAD+ dose groups were lower than those in the HF group. Medium and highdose NAD+ showed superior positive effects on myocardial hypertrophy, cardiac function, and myocardial fibrosis and reduced the MI rate.

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[1]
Konstantinides, S.V. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the european respiratory society (ERS): The task force for the diagnosis and management of acute pulmonary embolism of the european society of cardiology (ESC). Eur Respir J, 2019, 54(3)
[2]
Dassanayaka, S.; Jones, S.P. Recent developments in heart failure. Circ. Res., 2015, 117(7), e58-e63.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.305765] [PMID: 26358111]
[3]
Pagliaro, B.R.; Cannata, F.; Stefanini, G.G.; Bolognese, L. Myocardial ischemia and coronary disease in heart failure. Heart Fail. Rev., 2020, 25(1), 53-65.
[http://dx.doi.org/10.1007/s10741-019-09831-z] [PMID: 31332663]
[4]
Sukoyan, G.V.; Kavadze, I.K. Effect of nadcin on energy supply system and apoptosis in ischemia-reperfusion injury to the myocardium. Bull. Exp. Biol. Med., 2008, 146(3), 321-324.
[http://dx.doi.org/10.1007/s10517-008-0268-2] [PMID: 19240850]
[5]
Roger, V.L. Epidemiology of heart failure. Circ. Res., 2013, 113(6), 646-659.
[http://dx.doi.org/10.1161/CIRCRESAHA.113.300268] [PMID: 23989710]
[6]
Anderson, J.L.; Morrow, D.A. Acute myocardial infarction. N. Engl. J. Med., 2017, 376(21), 2053-2064.
[http://dx.doi.org/10.1056/NEJMra1606915] [PMID: 28538121]
[7]
Sun, J.; Xu, W.; Hua, H.; Xiao, Y.; Chen, X.; Gao, Z.; Li, S.; Jing, X.; Du, F.; Sun, G. Pharmacodynamic and pharmacokinetic effects of S086, a novel angiotensin receptor neprilysin inhibitor. Biomed. Pharmacother., 2020, 129, 110410.
[http://dx.doi.org/10.1016/j.biopha.2020.110410] [PMID: 32570118]
[8]
Braunwald, E. The war against heart failure: The lancet lecture. Lancet, 2015, 385(9970), 812-824.
[http://dx.doi.org/10.1016/S0140-6736(14)61889-4] [PMID: 25467564]
[9]
O’Gara, P.T.; Kushner, F.G.; Ascheim, D.D.; Casey, D.E., Jr; Chung, M.K.; de Lemos, J.A.; Ettinger, S.M.; Fang, J.C.; Fesmire, F.M.; Franklin, B.A.; Granger, C.B.; Krumholz, H.M.; Linderbaum, J.A.; Morrow, D.A.; Newby, L.K.; Ornato, J.P.; Ou, N.; Radford, M.J.; Tamis-Holland, J.E.; Tommaso, C.L.; Tracy, C.M.; Woo, Y.J.; Zhao, D.X. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: A report of the american college of cardiology foundation/american heart association task force on practice guidelines. J. Am. Coll. Cardiol., 2013, 61(4), 485-510.
[http://dx.doi.org/10.1016/j.jacc.2012.11.018] [PMID: 23256913]
[10]
Lloyd-Jones, D.; Adams, R.; Carnethon, M.; De Simone, G.; Ferguson, T.B.; Flegal, K.; Ford, E.; Furie, K.; Go, A.; Greenlund, K.; Haase, N.; Hailpern, S.; Ho, M.; Howard, V.; Kissela, B.; Kittner, S.; Lackland, D.; Lisabeth, L.; Marelli, A.; McDermott, M.; Meigs, J.; Mozaffarian, D.; Nichol, G.; O’Donnell, C.; Roger, V.; Rosamond, W.; Sacco, R.; Sorlie, P.; Stafford, R.; Steinberger, J.; Thom, T.; Wasserthiel-Smoller, S.; Wong, N.; Wylie-Rosett, J.; Hong, Y. Heart disease and stroke statistics--2009 update: A report from the american heart association statistics committee and stroke statistics subcommittee. Circulation, 2009, 119(3), 480-486.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.191259] [PMID: 19171871]
[11]
Mericskay, M. Nicotinamide adenine dinucleotide homeostasis and signalling in heart disease: Pathophysiological implications and therapeutic potential. Arch. Cardiovasc. Dis., 2016, 109(3), 207-215.
[http://dx.doi.org/10.1016/j.acvd.2015.10.004] [PMID: 26707577]
[12]
Zhou, B.; Tian, R. Mitochondrial dysfunction in pathophysiology of heart failure. J. Clin. Invest., 2018, 128(9), 3716-3726.
[http://dx.doi.org/10.1172/JCI120849] [PMID: 30124471]
[13]
Sukoyan, G.V.; Andriadze, N.A.; Guchua, E.I.; Karsanov, N.V. Effect of NAD on recovery of adenine nucleotide pool, phosphorylation potential, and stimulation of apoptosis during late period of reperfusion damage to myocardium. Bull. Exp. Biol. Med., 2005, 139(1), 46-49.
[http://dx.doi.org/10.1007/s10517-005-0208-3] [PMID: 16142273]
[14]
Wang, J.; Tang, Y.; Lv, X.; Zhang, J.; Ma, B.; Wen, X.; Bao, Y.; Wang, G. Corrigendum: “Tectoridin inhibits osteoclastogenesis and bone loss in a murine model of ovariectomy-induced osteoporosis”. Exp. Gerontol., 2023, 180, 112251.
[http://dx.doi.org/10.1016/j.exger.2023.112251] [PMID: 37487835]
[15]
Breton, M.; Costemale-Lacoste, J.F.; Li, Z.; Lafuente-Lafuente, C.; Belmin, J.; Mericskay, M. Blood NAD levels are reduced in very old patients hospitalized for heart failure. Exp. Gerontol., 2020, 139, 111051.
[http://dx.doi.org/10.1016/j.exger.2020.111051] [PMID: 32783906]
[16]
Tannous, C.; Ghali, R.; Karoui, A.; Habeichi, N.J.; Amin, G.; Booz, G.W.; Mericskay, M.; Refaat, M.; Zouein, F.A. Nicotinamide riboside supplementation restores myocardial nicotinamide adenine dinucleotide levels, improves survival, and promotes protective environment post myocardial infarction. Cardiovasc. Drugs Ther., 2023.
[http://dx.doi.org/10.1007/s10557-023-07525-1] [PMID: 37999834]
[17]
Diguet, N.; Trammell, S.A.J.; Tannous, C.; Deloux, R.; Piquereau, J.; Mougenot, N.; Gouge, A.; Gressette, M.; Manoury, B.; Blanc, J.; Breton, M.; Decaux, J.F.; Lavery, G.G.; Baczkó, I.; Zoll, J.; Garnier, A.; Li, Z.; Brenner, C.; Mericskay, M. Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy. Circulation, 2018, 137(21), 2256-2273.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.026099] [PMID: 29217642]
[18]
Lee, C.F.; Chavez, J.D.; Garcia-Menendez, L.; Choi, Y.; Roe, N.D.; Chiao, Y.A.; Edgar, J.S.; Goo, Y.A.; Goodlett, D.R.; Bruce, J.E.; Tian, R. Normalization of NAD + redox balance as a therapy for heart failure. Circulation, 2016, 134(12), 883-894.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022495] [PMID: 27489254]
[19]
Yamamoto, T.; Byun, J.; Zhai, P.; Ikeda, Y.; Oka, S.; Sadoshima, J. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One, 2014, 9(6), e98972.
[http://dx.doi.org/10.1371/journal.pone.0098972] [PMID: 24905194]
[20]
Xiao, Y.; Phelp, P.; Wang, Q.; Bakker, D.; Nederlof, R.; Hollmann, M.W.; Zuurbier, C.J. Cardioprotecive properties of known agents in rat ischemia-reperfusion model under clinically relevant conditions: only the nad precursor nicotinamide riboside reduces infarct size in presence of fentanyl, midazolam and cangrelor, but not propofol. Front. Cardiovasc. Med., 2021, 8, 712478.
[http://dx.doi.org/10.3389/fcvm.2021.712478] [PMID: 34527711]
[21]
Nadtochiy, S.M.; Wang, Y.T.; Nehrke, K.; Munger, J.; Brookes, P.S. Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH. J. Mol. Cell. Cardiol., 2018, 121, 155-162.
[http://dx.doi.org/10.1016/j.yjmcc.2018.06.007] [PMID: 29958828]
[22]
von Lueder, T.G.; Wang, B.H.; Kompa, A.R.; Huang, L.; Webb, R.; Jordaan, P.; Atar, D.; Krum, H. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ. Heart Fail., 2015, 8(1), 71-78.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.001785] [PMID: 25362207]
[23]
Ishii, M.; Kaikita, K.; Sato, K.; Sueta, D.; Fujisue, K.; Arima, Y.; Oimatsu, Y.; Mitsuse, T.; Onoue, Y.; Araki, S.; Yamamuro, M.; Nakamura, T.; Izumiya, Y.; Yamamoto, E.; Kojima, S.; Kim-Mitsuyama, S.; Ogawa, H.; Tsujita, K. Cardioprotective effects of LCZ696 (sacubitril/valsartan) after experimental acute myocardial infarction. JACC Basic Transl. Sci., 2017, 2(6), 655-668.
[http://dx.doi.org/10.1016/j.jacbts.2017.08.001] [PMID: 30062181]
[24]
Zhang, Y.; Wang, B.; Fu, X.; Guan, S.; Han, W.; Zhang, J.; Gan, Q.; Fang, W.; Ying, W.; Qu, X. Exogenous NAD(+) administration significantly protects against myocardial ischemia/reperfusion injury in rat model. Am. J. Transl. Res., 2016, 8(8), 3342-3350.
[PMID: 27648125]
[25]
Liu, L.; Wang, Q.; Zhao, B.; Wu, Q.; Wang, P. Exogenous nicotinamide adenine dinucleotide administration alleviates ischemia/reperfusion-induced oxidative injury in isolated rat hearts via Sirt5-SDH-succinate pathway. Eur. J. Pharmacol., 2019, 858, 172520.
[http://dx.doi.org/10.1016/j.ejphar.2019.172520] [PMID: 31278893]
[26]
Yan, P.; Mao, W.; Jin, L.; Fang, M.; Liu, X.; Lang, J.; Jin, L.; Cao, B.; Shou, Q.; Fu, H. Crude radix aconiti lateralis preparata (Fuzi) with Glycyrrhiza reduces inflammation and ventricular remodeling in mice through the TLR4/NF-κB pathway. Mediators Inflamm., 2020, 2020, 1-13.
[http://dx.doi.org/10.1155/2020/5270508] [PMID: 33132755]
[27]
Chioncel, O.; Lainscak, M.; Seferovic, P.M.; Anker, S.D.; Crespo-Leiro, M.G.; Harjola, V.P.; Parissis, J.; Laroche, C.; Piepoli, M.F.; Fonseca, C.; Mebazaa, A.; Lund, L.; Ambrosio, G.A.; Coats, A.J.; Ferrari, R.; Ruschitzka, F.; Maggioni, A.P.; Filippatos, G. Epidemiology and one‐year outcomes in patients with chronic heart failure and preserved, mid‐range and reduced ejection fraction: An analysis of the ESC Heart Failure Long‐Term Registry. Eur. J. Heart Fail., 2017, 19(12), 1574-1585.
[http://dx.doi.org/10.1002/ejhf.813] [PMID: 28386917]
[28]
Yusuf, S.; Pitt, B.; Davis, C.E.; Hood, W.B.; Cohn, J.N. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N. Engl. J. Med., 1991, 325(5), 293-302.
[http://dx.doi.org/10.1056/NEJM199108013250501] [PMID: 2057034]
[29]
The cardiac insufficiency bisoprolol study II (CIBIS-II) a randomised trial. Lancet, 1999, 353(9146), 9-13.
[http://dx.doi.org/10.1016/S0140-6736(98)11181-9] [PMID: 10023943]
[30]
Pitt, B.; Zannad, F.; Remme, W.J.; Cody, R.; Castaigne, A.; Perez, A.; Palensky, J.; Wittes, J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med., 1999, 341(10), 709-717.
[http://dx.doi.org/10.1056/NEJM199909023411001] [PMID: 10471456]
[31]
Granger, C.B.; McMurray, J.J.V.; Yusuf, S.; Held, P.; Michelson, E.L.; Olofsson, B.; Östergren, J.; Pfeffer, M.A.; Swedberg, K. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: The CHARM-Alternative trial. Lancet, 2003, 362(9386), 772-776.
[http://dx.doi.org/10.1016/S0140-6736(03)14284-5] [PMID: 13678870]
[32]
McMurray, J.J.V.; Packer, M.; Desai, A.S.; Gong, J.; Lefkowitz, M.P.; Rizkala, A.R.; Rouleau, J.L.; Shi, V.C.; Solomon, S.D.; Swedberg, K.; Zile, M.R. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N. Engl. J. Med., 2014, 371(11), 993-1004.
[http://dx.doi.org/10.1056/NEJMoa1409077] [PMID: 25176015]
[33]
McMurray, J.J.V.; Solomon, S.D.; Inzucchi, S.E.; Køber, L.; Kosiborod, M.N.; Martinez, F.A.; Ponikowski, P.; Sabatine, M.S.; Anand, I.S.; Bělohlávek, J.; Böhm, M.; Chiang, C.E.; Chopra, V.K.; de Boer, R.A.; Desai, A.S.; Diez, M.; Drozdz, J.; Dukát, A.; Ge, J.; Howlett, J.G.; Katova, T.; Kitakaze, M.; Ljungman, C.E.A.; Merkely, B.; Nicolau, J.C.; O’Meara, E.; Petrie, M.C.; Vinh, P.N.; Schou, M.; Tereshchenko, S.; Verma, S.; Held, C.; DeMets, D.L.; Docherty, K.F.; Jhund, P.S.; Bengtsson, O.; Sjöstrand, M.; Langkilde, A.M. Dapagliflozin in patients with heart failure and reduced ejection fraction. N. Engl. J. Med., 2019, 381(21), 1995-2008.
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[34]
Taegtmeyer, H. Cardiac metabolism as a target for the treatment of heart failure. Circulation, 2004, 110(8), 894-896.
[http://dx.doi.org/10.1161/01.CIR.0000139340.88769.D5] [PMID: 15326079]
[35]
Yoshino, J.; Baur, J.A.; Imai, S. NAD+ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metab., 2018, 27(3), 513-528.
[http://dx.doi.org/10.1016/j.cmet.2017.11.002] [PMID: 29249689]
[36]
Rajman, L.; Chwalek, K.; Sinclair, D.A. Therapeutic potential of NAD-boosting molecules: The in vivo evidence. Cell Metab., 2018, 27(3), 529-547.
[http://dx.doi.org/10.1016/j.cmet.2018.02.011] [PMID: 29514064]
[37]
Hershberger, K.A.; Martin, A.S.; Hirschey, M.D. Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases. Nat. Rev. Nephrol., 2017, 13(4), 213-225.
[http://dx.doi.org/10.1038/nrneph.2017.5] [PMID: 28163307]
[38]
Walsh, M.N.; Yancy, C.W.; Albert, N.M.; Curtis, A.B.; Stough, W.G.; Gheorghiade, M.; Heywood, J.T.; McBride, M.L.; Mehra, M.R.; O’Connor, C.M.; Reynolds, D.; Fonarow, G.C. Electronic health records and quality of care for heart failure. Am. Heart J., 2010, 159(4), 635-642.e1.
[http://dx.doi.org/10.1016/j.ahj.2010.01.006] [PMID: 20362723]
[39]
Suzuki, G.; Morita, H.; Mishima, T.; Sharov, V.G.; Todor, A.; Tanhehco, E.J.; Rudolph, A.E.; McMahon, E.G.; Goldstein, S.; Sabbah, H.N. Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation, 2002, 106(23), 2967-2972.
[http://dx.doi.org/10.1161/01.CIR.0000039104.56479.42] [PMID: 12460880]
[40]
Gajarsa, J.J.; Kloner, R.A. Left ventricular remodeling in the post-infarction heart: A review of cellular, molecular mechanisms, and therapeutic modalities. Heart Fail. Rev., 2011, 16(1), 13-21.
[http://dx.doi.org/10.1007/s10741-010-9181-7] [PMID: 20623185]
[41]
Struthers, A.D. Pathophysiology of heart failure following myocardial infarction. Heart, 2005, 91(Suppl 2), ii14-6-ii43-8.
[http://dx.doi.org/10.1136/hrt.2005.062034]
[42]
Fedak, P.W.M.; Verma, S.; Weisel, R.D.; Li, R.K. Cardiac remodeling and failure. Cardiovasc. Pathol., 2005, 14(1), 1-11.
[http://dx.doi.org/10.1016/j.carpath.2004.12.002] [PMID: 15710285]

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