Molecular Understanding of the Cardiomodulation in Myocardial Infarction and the Mechanism of Vitamin E Protections

Author(s): Khairul Anwar Zarkasi, Tan Jen-Kit, Zakiah Jubri*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 17 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Myocardial infarction is a major cause of deaths globally. Modulation of several molecular mechanisms occurs during the initial stages of myocardial ischemia prior to permanent cardiac tissue damage, which involves both pathogenic as well as survival pathways in the cardiomyocyte. Currently, there is increasing evidence regarding the cardioprotective role of vitamin E in alleviating the disease. This fat-soluble vitamin does not only act as a powerful antioxidant; but it also has the ability to regulate several intracellular signalling pathways including HIF-1, PPAR-γ, Nrf-2, and NF-κB that influence the expression of a number of genes and their protein products. Essentially, it inhibits the molecular progression of tissue damage and preserves myocardial tissue viability. This review aims to summarize the molecular understanding of the cardiomodulation in myocardial infarction as well as the mechanism of vitamin E protection.

Keywords: Myocardial infarction, vitamin E, tocopherol, tocotrienol, cardiomodulation, CHD.

Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Simoons, M.L.; Chaitman, B.R.; White, H.D.; Katus, H.A.; Apple, F.S.; Lindahl, B.; Morrow, D.A.; Chaitman, B.A.; Clemmensen, P.M.; Johanson, P.; Hod, H.; Underwood, R.; Bax, J.J.; Bonow, R.O.; Pinto, F.; Gibbons, R.J.; Fox, K.A.; Atar, D.; Newby, L.K.; Galvani, M.; Hamm, C.W.; Uretsky, B.F.; Steg, P.G.; Wijns, W.; Bassand, J.P.; Menasché, P.; Ravkilde, J.; Ohman, E.M.; Antman, E.M.; Wallentin, L.C.; Armstrong, P.W.; Simoons, M.L.; Januzzi, J.L.; Nieminen, M.S.; Gheorghiade, M.; Filippatos, G.; Luepker, R.V.; Fortmann, S.P.; Rosamond, W.D.; Levy, D.; Wood, D.; Smith, S.C.; Hu, D.; Lopez-Sendon, J.L.; Robertson, R.M.; Weaver, D.; Tendera, M.; Bove, A.A.; Parkhomenko, A.N.; Vasilieva, E.J.; Mendis, S. Third universal definition of myocardial infarction. Eur. Heart J., 2012, 33(20), 2551-2567.
Zafari, A.M.; Abdou, M.H. Myocardial Infarction., (Accessed Aug 15, 2017).
Sanchis-Gomar, F.; Perez-Quilis, C.; Leischik, R.; Lucia, A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann. Transl. Med., 2016, 4(13), 256-256.
The National Health Service Coronary Heart Disease.. (Accessed Aug 23, 2017)
World Health Organization (WHO).. Cardiovascular Diseases (CVDs): Fact Sheet. fs317/en/ (Accessed Aug 24, 2017)
Finegold, J.A.; Asaria, P.; Francis, D.P. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int. J. Cardiol., 2013, 168(2), 934-945.
Roth, G.A.; Huffman, M.D.; Moran, A.E.; Feigin, V.; Mensah, G.A.; Naghavi, M.; Murray, C.J.L. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation, 2015, 132(17), 1667-1678.
Roth, G.A.; Johnson, C.; Abajobir, A.; Abd-Allah, F.; Abera, S.F.; Abyu, G.; Ahmed, M.; Aksut, B.; Alam, T.; Alam, K. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J. Am. Coll. Cardiol., 2017, 70(1), 1-25.
World Health Organization. Non-communicable Diseases in the South-East Asia Region: Situation and Response. WHO Regional Office for South-East Asia, 2011.
Department of Statistics Malaysia. Statistics on Causes of Death, Malaysia,. 2014. r=column/cthemeByCat&cat=401&bul_id=eTY2NW00S3BLb1dldWJmVFNMWmphQT09&menu_id=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09 (Accessed Sep 21, 2017)
Farlex. Medical Dictionary for the Health Professions and Nursing.. (Accessed Feb 27, 2018)
Haber, E.P.; Procópio, J.; Carvalho, C.R.O.; Carpinelli, A.R.; Newsholme, P.; Curi, R. New insights into fatty acid modulation of pancreatic β-cell function. Int. Rev. Cytol., 2006, 248, 1-41.
DeSantis, D.A.; Ko, C.; Liu, Y.; Liu, X.; Hise, A.G.; Nunez, G.; Croniger, C.M. Alcohol-induced liver injury is modulated by Nlrp3 and Nlrc4 inflammasomes in mice. Mediators Inflamm., 2013, 2013751374
Livero, F.A.; Acco, A. Molecular basis of alcoholic fatty liver disease: from incidence to treatment. Hepatol. Res., 2016, 46(1), 111-123.
Song, X.; Qian, X.; Shen, M.; Jiang, R.; Wagner, M.B.; Ding, G.; Chen, G.; Shen, B. Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression. Biochim. Biophys. Acta Mol. Cell Res., 2015, 1853(2), 513-521.
Touyz, R.M.; Fareh, J.; Thibault, G.; Schiffrin, E.L. Intracellular Ca2+ modulation by angiotensin II and endothelin-1 in cardiomyocytes and fibroblasts from hypertrophied hearts of spontaneously hypertensive rats. Hypertens., 1996, 28(5), 797-805.
Kolwicz, S.C.; Purohit, S.; Tian, R. Cardiac metabolism and its interactions with contraction, growth, and survival of the cardiomyocte. Circ. Res., 2013, 113(5)
Lopaschuk, G.D.; Ussher, J.R. Evolving concepts of myocardial energy metabolism. Circ. Res., 2016, 119(11), 1173-1176.
Fillmore, N.; Mori, J.; Lopaschuk, G.D. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br. J. Pharmacol., 2014, 171(8), 2080-2090.
Mashek, D.G.; Li, L.O.; Coleman, R.A. Long-chain acyl-Coa synthetases and fatty acid channeling. Future Lipidol., 2007, 2(4), 465-476.
Rufer, A.C.; Thoma, R.; Benz, J.; Stihle, M.; Gsell, B.; De Roo, E.; Banner, D.W.; Mueller, F.; Chomienne, O.; Hennig, M. The crystal structure of carnitine palmitoyltransferase 2 and implications for diabetes treatment. Structure, 2006, 14(4), 713-723.
Nsiah-Sefaa, A.; McKenzie, M. Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease. Biosci. Rep., 2016, 36(2)e00313
Doenst, T.; Nguyen, T.D.; Abel, E.D. Cardiac metabolism in heart failure: implications beyond ATP production. Circ. Res., 2013, 113(6), 709-724.
Shao, D.; Tian, R. Glucose transporters in cardiac metabolism and hypertrophy. Compr. Physiol., 2016, 6(1), 331-351.
Patel, K.P.; O’Brien, T.W.; Subramony, S.H.; Shuster, J.; Stacpoole, P.W. The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients. Mol. Genet. Metab., 2012, 106(3), 385-394.
Depre, C.; Vanoverschelde, J.L.; Taegtmeyer, H. Glucose for the heart. Circulation, 1999, 99(4), 578-588.
Rodwell, V.W.; Botham, K.M.; Kennelly, P.J.; Weil, P.A.; Bender, D.A. Harper’s Illustrated Biochemistry, 30th ed; McGraw-Hill Education LLC: New York, 2015.
Mailloux, R.J. Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species. Redox Biol., 2015, 4, 381-398.
Chapman, A.R.; Adamson, P.D.; Mills, N.L. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart, 2017, 103(1), 10-18.
Whitmer, J.T.; Idell-Wenger, J.A.; Rovetto, M.J.; Neely, J.R. Control of fatty acid metabolism in ischemic and hypoxic hearts. J. Biol. Chem., 1978, 253(12), 4305-4309.
Stanley, W.C. Myocardial energy metabolism during ischemia and the mechanisms of metabolic therapies. J. Cardiovasc. Pharmacol. Ther., 2004, 9(Suppl. 1), S31-S45.
Mitra, A.; Basak, T.; Ahmad, S.; Datta, K.; Datta, R.; Sengupta, S.; Sarkar, S. Comparative proteome profiling during cardiac hypertrophy and myocardial infarction reveals altered glucose oxidation by differential activation of pyruvate dehydrogenase E1 component subunit β. J. Mol. Biol., 2015, 427(11), 2104-2120.
Vermeulen, R.P.; Hoekstra, M.; Nijsten, M.W.; van der Horst, I.C.; van Pelt, L.J.; Jessurun, G.A.; Jaarsma, T.; Zijlstra, F.; van den Heuvel, A.F. Clinical correlates of arterial lactate levels in patients with ST-segment elevation myocardial infarction at admission: A descriptive study. Crit. Care, 2010, 14, R164.
Gandhi, A.A.; Akholkar, P.J. Metabolic acidosis in acute myocardial infarction. Int. J. Adv. Med., 2015, 2(3), 260-263.
Jentzer, J.C.; Chonde, M.D.; Dezfulian, C. Myocardial dysfunction and shock after cardiac arrest. BioMed Res. Int., 2015, 2015314796
Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Cell biology of ischemia/reperfusion injury. Int. Rev. Cell Mol. Biol., 2012, 298, 229-317.
Bell, J.R.; Vila-Petroff, M.; Delbridge, L.M.D. CaMKII-dependent responses to ischemia and reperfusion challenges in the heart. Front. Pharmacol., 2014, 5, 96.
Pinnell, J.; Turner, S.; Howell, S. Cardiac muscle physiology. Contin. Educ. Anaesth. Crit. Care Pain, 2007, 7(3), 85-88.
Sanada, S.; Komuro, I.; Kitakaze, M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. AJP Hear. Circ. Physiol., 2011, 301(5), H1723-H1741.
Ibáñez, B.; Heusch, G.; Ovize, M.; Van de Werf, F. Evolving therapies for myocardial ischemia/reperfusion injury. J. Am. Coll. Cardiol., 2015, 65(14), 1454-1471.
Wei, B.; You, M.G.; Ling, J.J.; Wei, L.L.; Wang, K.; Li, W.W.; Chen, T.; Du, Q.M.; Ji, H. Regulation of antioxidant system, lipids and fatty acid β-oxidation contributes to the cardioprotective effect of sodium tanshinone IIA sulphonate in isoproterenol-induced myocardial infarction in rats. Atherosclerosis, 2013, 230(1), 148-156.
Snyder, C.M.; Chandel, N.S. Mitochondrial regulation of cell survival and death during low-oxygen conditions. Antioxid. Redox Signal., 2009, 11(11), 2673-2683.
Semenza, G.L. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci. STKE, 2007, 2007(407), cm8-cm8.
Dengler, V.L.; Galbraith, M.; Espinosa, J.M. Transcriptional regulation by hypoxia inducible factors. Crit. Rev. Biochem. Mol. Biol., 2014, 49(1), 1-15.
Jiang, B.; Dong, H.; Zhang, Z.; Wang, W.; Zhang, Y.; Xu, X. Hypoxic response elements control expression of human vascular endothelial growth factor (165) genes transferred to ischemia myocardium in vivo and in vitro. J. Gene Med., 2007, 9(9), 788-796.
Ruas, J.L.; Berchner-Pfannschmidt, U.; Malik, S.; Gradin, K.; Fandrey, J.; Roeder, R.G.; Pereira, T.; Poellinger, L. Complex regulation of the transactivation function of hypoxia-inducible factor-1 alpha by direct interaction with two distinct domains of the CREB-binding protein/P300. J. Biol. Chem., 2010, 285(4), 2601-2609.
Sharp, F.R.; Bernaudin, M. HIF-1 and oxygen sensing in the brain. Nat. Rev. Neurosci., 2004, 5(6), 437-448.
Krishnan, J.; Suter, M.; Windak, R.; Krebs, T.; Felley, A.; Montessuit, C.; Tokarska-Schlattner, M.; Aasum, E.; Bogdanova, A.; Perriard, E. Activation of a HIF-1α-PPARγ axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab., 2009, 9(6), 512-524.
Masson, N.; Singleton, R.S.; Sekirnik, R.; Trudgian, D.C.; Ambrose, L.J.; Miranda, M.X.; Tian, Y-M.; Kessler, B.M.; Schofield, C.J.; Ratcliffe, P.J. The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity. EMBO Rep., 2012, 13(3), 251-257.
Huang, M.; Nguyen, P.; Jia, F.; Hu, S.; Gong, Y.; De Almeida, P.E.; Wang, L.; Nag, D.; Kay, M.A.; Giaccia, A.J.; Robbins, R.C.; Wu, J.C. Double knockdown of prolyl hydroxylase and factor-inhibiting hypoxia-inducible factor with nonviral minicircle gene therapy enhances stem cell mobilization and angiogenesis after myocardial infarction. Circulation, 2011, 124(11)(Suppl. 1), S46-S54.
Lee, S.H.; Wolf, P.L.; Escudero, R.; Deutsch, R.; Jamieson, S.W.; Thistlethwaite, P.A. Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N. Engl. J. Med., 2000, 342(9), 626-633.
Hyvärinen, J.; Hassinen, I.E.; Sormunen, R.; Mäki, J.M.; Kivirikko, K.I.; Koivunen, P.; Myllyharju, J. Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury. J. Biol. Chem., 2010, 285(18), 13646-13657.
Miró-Murillo, M.; Elorza, A.; Soro-Arnáiz, I.; Albacete-Albacete, L.; Ordoñez, A.; Balsa, E.; Vara-Vega, A.; Vázquez, S.; Fuertes, E.; Fernández-Criado, C.; Landázuri, M.O.; Aragonés, J. Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression. PLoS One, 2011, 6(7)e22589
Kussmaul, L.; Hirst, J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc. Natl. Acad. Sci. USA, 2006, 103(20), 7607-7612.
Heather, L.C.; Carr, C.A.; Stuckey, D.J.; Pope, S.; Morten, K.J.; Carter, E.E.; Edwards, L.M.; Clarke, K. Critical role of complex III in the early metabolic changes following myocardial infarction. Cardiovasc. Res., 2010, 85(1), 127-136.
Paradies, G.; Petrosillo, G.; Pistolese, M.; Di Venosa, N.; Federici, A.; Ruggiero, F.M. Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart. Circ. Res., 2004, 94(1), 53-59.
Murphy, M.P. How mitochondria produce reactive oxygen species. Biochem. J., 2009, 417(1), 1-13.
Meitzler, J.L.; Antony, S.; Wu, Y.; Juhasz, A.; Liu, H.; Jiang, G.; Lu, J.; Roy, K.; Doroshow, J.H. NADPH oxidases: A perspective on reactive oxygen species production in tumor biology. Antioxid. Redox Signal., 2014, 20(17), 2873-2889.
Lassègue, B.; San Martín, A.; Griendling, K.K. Biochemistry, physiology and pathophysiology of NADPH oxidases in the cardiovascular system. Circ. Res., 2012, 110(10), 1364-1390.
Braunersreuther, V.; Montecucco, F.; Asrih, M.; Pelli, G.; Galan, K.; Frias, M.; Burger, F.; Quindere, A.L.G.; Montessuit, C.; Krause, K-H.; Mach, F.; Jaquet, V. Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury. J. Mol. Cell. Cardiol., 2013, 64, 99-107.
Kuroda, J.; Ago, T.; Matsushima, S.; Zhai, P.; Schneider, M.D.; Sadoshima, J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc. Natl. Acad. Sci. USA, 2010, 107(35), 1-6.
Tziomalos, K.; Hare, J.M. Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance. Front. Biosci., 2009, 14, 237-262.
Pandey, N.R.; Kaur, G.; Chandra, M.; Sanwal, G.G.; Misra, M.K. Enzymatic oxidant and antioxidants of human blood platelets in unstable angina and myocardial infarction. Int. J. Cardiol., 2000, 76, 33-38.
Chambers, D.E.; Parks, D.A.; Patterson, G.; Roy, R.; McCord, J.M.; Yoshida, S.; Parmley, L.F.; Downey, J.M. Xanthine oxidase as a source of free radical damage in myocardial ischemia. J. Mol. Cell. Cardiol., 1985, 17(2), 145-152.
Shintani, H. Determination of xanthine oxidase. Pharm. Anal. Acta, 2013, S7, 004.
Raghuvanshi, R.; Kaul, A.; Bhakuni, P.; Mishra, A.; Misra, M.K. Xanthine oxidase as a marker of myocardial infarction. Indian J. Clin. Biochem., 2007, 22(2), 90-92.
Singh, J.A.; Yu, S. Allopurinol reduces the risk of myocardial infarction (MI) in the elderly: A study of Medicare claims. Arthritis Res. Ther., 2016, 18, 209.
Strijdom, H.; Chamane, N.; Lochner, A. Nitric oxide in the cardiovascular system: A simple molecule with complex actions. Cardiovasc. J. Afr., 2009, 20(5), 303-310.
Janssens, S.; Pokreisz, P.; Schoonjans, L.; Pellens, M.; Vermeersch, P.; Tjwa, M.; Jans, P.; Scherrer-Crosbie, M.; Picard, M.H.; Szelid, Z.; Gillijns, H.; Van de Werf, F.; Collen, D.; Bloch, K.D. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ. Res., 2004, 94(9), 1256-1262.
Grandi, E.; Govoni, M.; Furini, S.; Severi, S.; Giordano, E.; Santoro, A.; Cavalcanti, S. Induction of NO synthase 2 in ventricular cardiomyocytes incubated with a conventional bicarbonate dialysis bath. Nephrol. Dial. Transplant., 2008, 23(7), 2192-2197.
Beigi, F.; Oskouei, B.N.; Zheng, M.; Cooke, C.A.; Lamirault, G.; Hare, J.M. Cardiac nitric oxide synthase-1 localization within the cardiomyocyte is accompanied by the adaptor protein, CAPON. Nitric Oxide, 2009, 21(3-4), 226-233.
Crane, B.R.; Arvai, A.S.; Ghosh, D.K.; Wu, C.; Getzoff, E.D.; Stuehr, D.J.; Tainer, J.A. Structure of nitric oxide synthase oxygenase dimer with pterin and substrate. Science, 1998, 279(5359), 2121-2126.
Ash, D.E. Structure and function of arginases. J. Nutr., 2004, 134(10), 2760S-2764S.
Harpster, M.H.; Bandyopadhyay, S.; Thomas, D.P.; Ivanov, P.S.; Keele, J.A.; Pineguina, N.; Gao, B.; Amarendran, V.; Gomelsky, M.; McCormick, R.J.; Stayton, M.M. Earliest changes in the left ventricular transcriptome postmyocardial infarction. Mamm. Genome, 2006, 17(7), 701-715.
Sankaralingam, S.; Arenas, I.A.; Lalu, M.M.; Davidge, S.T. Preeclampsia: current understanding of the molecular basis of vascular dysfunction. Expert Rev. Mol. Med., 2006, 8(3), 1-20.
Grönros, J.; Kiss, A.; Palmer, M.; Jung, C.; Berkowitz, D.; Pernow, J. Arginase inhibition improves coronary microvascular function and reduces infarct size following ischaemia-reperfusion in a rat model. Acta Physiol. , 2013, 208(2), 172-179.
Piñeiro, V.; Ortiz-Moreno, A.; Mora-Escobedo, R.; Hernandez-Navarro, M.D.; Ceballos-Reyes, G.; Chamorro-Cevallos, G. Effect of L-arginine oral supplementation on response to myocardial infarction in hypercholesterolemic and hypertensive rats. Plant Foods Hum. Nutr., 2010, 65, 31-37.
Kobayashi, A.; Kang, M-I.; Okawa, H.; Ohtsuji, M.; Zenke, Y.; Chiba, T.; Igarashi, K.; Yamamoto, M. Oxidative stress sensor keap1 functions as an adaptor for cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol., 2004, 24(16), 7130-7139.
Nioi, P.; McMahon, M.; Itoh, K.; Yamamoto, M.; Hayes, J.D. Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H: Quinone oxidoreductase 1 gene: Reassessment of the ARE consensus sequence. Biochem. J., 2003, 374(Pt 2), 337-348.
Gorrini, C.; Harris, I.S.; Mak, T.W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov., 2013, 12(12), 931-947.
Ma, Q. Role of Nrf2 in oxidative stress and toxicity. Annu. Rev. Pharmacol. Toxicol., 2013, 53, 401-426.
Fourquet, S.; Guerois, R.; Biard, D.; Toledano, M.B. Activation of NRF2 by nitrosative agents and H2O2 involves KEAP1 disulfide formation. J. Biol. Chem., 2010, 285(11), 8463-8471.
Rachakonda, G.; Xiong, Y.; Sekhar, K.R.; Stamer, S.L.; Liebler, D.C.; Freeman, M.L. Covalent modification at cys151 dissociates the electrophile sensor keap1 from the ubiquitin ligase CUL3. Chem. Res. Toxicol., 2008, 21(3), 705-710.
Li, H.; Xie, Y-H.; Yang, Q.; Wang, S-W.; Zhang, B-L.; Wang, J-B.; Cao, W.; Bi, L-L.; Sun, J-Y.; Miao, S.; Hu, J.; Zhou, X.X.; Qiu, P.C. Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats. PLoS One, 2012, 7(11)e48872
Strom, J.; Chen, Q.M. Loss of Nrf2 promotes rapid progression to heart failure following myocardial infarction. Toxicol. Appl. Pharmacol., 2017, 327, 52-58.
Xu, B.; Zhang, J.; Strom, J.; Lee, S.; Chen, Q.M. Myocardial ischemic reperfusion induces de novo Nrf2 protein translation. Biochim. Biophys. Acta, 2014, 1842(9), 1638-1647.
Tong, X.; Yin, L.; Washington, R.; Rosenberg, D.W.; Giardina, C. The p50-p50 NF-κB complex as a stimulus-specific repressor of gene activation. Mol. Cell. Biochem., 2004, 265(1-2), 171-183.
Zeng, M.; Yan, H.; Chen, Y.; Zhao, H.; Lv, Y.; Liu, C.; Zhou, P.; Zhao, B. Suppression of NF-κB reduces myocardial no-reflow. PLoS One, 2012, 7(10)e47306
Oeckinghaus, A.; Ghosh, S. The NF-κB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol., 2009, 1(4)a000034
Maier, H.J.; Schips, T.G.; Wietelmann, A.; Krüger, M.; Brunner, C.; Sauter, M.; Klingel, K.; Böttger, T.; Braun, T.; Wirth, T. Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure. Proc. Natl. Acad. Sci. USA, 2012, 109(29), 11794-11799.
Zambon, A.; Gervois, P.; Pauletto, P.; Fruchart, J-C.; Staels, B. Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-α activators. Arterioscler. Thromb. Vasc. Biol., 2006, 26(5), 977-986.
Pahl, H.L. Activators and target genes of Rel/NF-κB transcription factors. Oncogene, 1999, 18(49), 6853-6866.
Ruparelia, N.; Digby, J.E.; Jefferson, A.; Medway, D.J.; Neubauer, S.; Lygate, C.A.; Choudhury, R.P. Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus. Inflamm. Res., 2013, 62(5), 515-525.
Kamata, H.; Manabe, T.; Oka, S.; Kamata, K.; Hirata, H. Hydrogen peroxide activates IκB kinases through phosphorylation of serine residues in the activation loops. FEBS Lett., 2002, 519(1-3), 231-237.
Defer, N.; Azroyan, A.; Pecker, F.; Pavoine, C. TNFR1 and TNFR2 signaling interplay in cardiac myocytes. J. Biol. Chem., 2007, 282(49), 35564-35573.
Devin, A.; Cook, A.; Lin, Y.; Rodriguez, Y.; Kelliher, M.; Liu, Z. The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity, 2000, 12(4), 419-429.
Zhang, L.; Blackwell, K.; Altaeva, A.; Shi, Z.; Habelhah, H. TRAF2 phosphorylation promotes NF-κB-dependent gene expression and inhibits oxidative stress-induced cell death. Mol. Biol. Cell, 2011, 22, 128-140.
Bhatia, M. Apoptosis versus necrosis in acute pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286(2), G189-G196.
Hotchkiss, R.S.; Strasser, A.; McDunn, J.E.; Swanson, P.E. Cell death. N. Engl. J. Med., 2009, 361(16), 1570-1583.
Casey, T.M.; Arthur, P.G.; Bogoyevitch, M.A. Necrotic death without mitochondrial dysfunction-delayed death of cardiac myocytes following oxidative stress. Biochim. Biophys. Acta Mol. Cell Res., 2007, 1773(3), 342-351.
Krautwald, S.; Ziegler, E.; Rölver, L.; Linkermann, A.; Keyser, K.A.; Steen, P.; Wollert, K.C.; Korf-Klingebiel, M.; Kunzendorf, U. Effective blockage of both the extrinsic and intrinsic pathways of apoptosis in mice by TAT-CrmA. J. Biol. Chem., 2010, 285(26), 19997-20005.
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
Boatright, K.M.; Salvesen, G.S. Mechanisms of caspase activation. Curr. Opin. Cell Biol., 2003, 15(6), 725-731.
Borutaite, V.; Budriunaite, A.; Morkuniene, R.; Brown, G.C. Release of mitochondrial cytochrome c and activation of cytosolic caspases induced by myocardial ischaemia. Biochim. Biophys. Acta Mol. Basis Dis., 2001, 1537(2), 101-109.
Todor, A.; Sharov, V.G.; Tanhehco, E.J.; Silverman, N.; Bernabei, A.; Sabbah, H.N. Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol., 2002, 283(3), H990-H995.
Lakhani, S.A.; Masud, A.; Kuida, K.; Porter, G.A.; Booth, C.J.; Mehal, W.Z.; Inayat, I.; Flavell, R.A. Caspases 3 and 7: Key mediators of mitochondrial events of apoptosis. Science, 2006, 311(5762), 847-851.
Dumont, E.A.; Reutelingsperger, C.P.M.; Smits, J.F.M.; Daemen, M.J.A.P.; Doevendans, P.A.F.; Wellens, H.J.J.; Hofstra, L. Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart. Nat. Med., 2001, 7(12), 1352-1355.
Niu, X.; Brahmbhatt, H.; Mergenthaler, P.; Zhang, Z.; Sang, J.; Daude, M.; Ehlert, F.G.R.; Diederich, W.E.; Wong, E.; Zhu, W.; Pogmore, J.; Nandy, J.P.; Satyanarayana, M.; Jimmidi, R.K.; Arya, P.; Leber, B.; Lin, J.; Culmsee, C.; Yi, J.; Andrews, D.W. A Small-molecule inhibitor of Bax and Bak oligomerization prevents genotoxic cell death and promotes neuroprotection. Cell Chem. Biol., 2017, 24(4), 493-506.e5.
Li, H.; Zhu, H.; Xu, C.; Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998, 94(4), 491-501.
Haudek, S.B.; Taffet, G.E.; Schneider, M.D.; Mann, D.L. TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. J. Clin. Invest., 2007, 117(9), 2692-2701.
Fauconnier, J.; Meli, A.C.; Thireau, J.; Roberge, S.; Shan, J.; Sassi, Y.; Reiken, S.R.; Rauzier, J-M.; Marchand, A.; Chauvier, D.; Cassan, C.; Crozier, C.; Bideaux, P.; Lompré, A.M.; Jacotot, E.; Marks, A.R.; Lacampagne, A. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc. Natl. Acad. Sci. USA, 2011, 108(32), 13258-13263.
Sharma, G.P.; Varley, K.G.; Kim, S.W.; Barwinsky, J.; Cohen, M.; Dhalla, N.S. Alterations in energy metabolism and ultrastructure upon reperfusion of the ischemic myocardium after coronary occlusion. Am. J. Cardiol., 1975, 36(2), 234-243.
Schmiedl, A.; Schnabel, P.A.; Mall, G.; Gebhard, M.M.; Hunneman, D.H.; Richter, J.; Bretschneider, H.J. The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling. Correlations during the course of myocardial global ischaemia. Virchows Arch. A Pathol. Anat. Histopathol., 1990, 416(4), 305-315.
Yanagiya, N.; Usuda, N.; Hayashi, K.; Nagata, T. Ultrastructural changes in myocardial and endothelial cells in the microvasculature of the rat heart after global ischemia. Med. Electron Microsc., 1994, 27(2), 73-79.
Filho, H.G.L.; Ferreira, N.L.; de Sousa, R.B.; de Carvalho, E.R.; Lobo, P.L.D.; Filho, J.G.L. Experimental model of myocardial infarction induced by isoproterenol in rats. Rev. Bras. Cir. Cardiovasc., 2011, 26(3), 469-476.
Burke, A.P. Pathology of Acute Myocardial Infarction.,
Peh, H.Y.; Tan, W.S.D.; Liao, W.; Wong, W.S.F. Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol. Pharmacol. Ther., 2016, 162, 152-169.
Ahsan, H.; Ahad, A.; Siddiqui, W.A. A review of characterization of tocotrienols from plant oils and foods. J. Chem. Biol., 2015, 8(2), 45-59.
Yamamoto, Y.; Fujisawa, A.; Hara, A.; Dunlap, W.C. An unusual vitamin E constituent (α-tocomonoenol) provides enhanced antioxidant protection in marine organisms adapted to cold-water environments. Proc. Natl. Acad. Sci. USA, 2001, 98(23), 13144-13148.
Ng, M.H.; Choo, Y.M.; Ma, A.N.; Chuah, C.H.; Hashim, M.A. Separation of vitamin E (tocopherol, tocotrienol, and tocomonoenol) in palm oil. Lipids, 2004, 39(10), 1031-1035.
Aggarwal, B.B.; Sundaram, C.; Prasad, S.; Kannappan, R. Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases. Biochem. Pharmacol., 2010, 80(11), 1613-1631.
Saito, Y.; Yoshida, Y.; Nishio, K.; Hayakawa, M.; Niki, E. Characterization of cellular uptake and distribution of vitamin E. Ann. N. Y. Acad. Sci., 2004, 1031, 368-375.
Serbinova, E.; Kagan, V.; Han, D.; Packer, L. Free radical recycling and intramembrane mobility in the antioxidant properties of α-tocopherol and α-tocotrienol. Free Radic. Biol. Med., 1991, 10(5), 263-275.
Fairus, S.; Nor, R.M.; Cheng, H.M.; Sundram, K. Postprandial metabolic fate of tocotrienol-rich vitamin E differs significantly from that of α-tocopherol. Am. J. Clin. Nutr., 2006, 84(4), 835-842.
Borel, P.; Pasquier, B.; Armand, M.; Tyssandier, V.; Grolier, P.; Alexandre-Gouabau, M.C.; Andre, M.; Senft, M.; Peyrot, J.; Jaussan, V.; Lairon, D.; Azais-Braesco, V. Processing of vitamin A and E in the human gastrointestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 280, G95-G103.
Schmölz, L.; Birringer, M.; Lorkowski, S.; Wallert, M. Complexity of vitamin E metabolism. World J. Biol. Chem., 2016, 7, 14-43.
Reboul, E.; Klein, A.; Bietrix, F.; Gleize, B.; Malezet-Desmoulins, C.; Schneider, M.; Margotat, A.; Lagrost, L.; Collet, X.; Borel, P. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J. Biol. Chem., 2006, 281(8), 4739-4745.
Abuasal, B.S.; Qosa, H.; Sylvester, P.W.; Kaddoumi, A. Comparison of the intestinal absorption and bioavailability of gamma-tocotrienol and alpha-tocopherol: In vitro, in situ and in vivo studies. Biopharm. Drug Dispos., 2012, 33(5), 246-256.
Dixon, J.B. Mechanisms of chylomicron uptake into lacteals. Ann. N. Y. Acad. Sci., 2010, 1207(Suppl. 1), E52-E57.
Reboul, E.; Trompier, D.; Moussa, M.; Klein, A.; Landrier, J-F.; Chimini, G.; Borel, P. ATP-binding cassette transporter A1 is significantly involved in the intestinal absorption of alpha- and gamma-tocopherol but not in that of retinyl palmitate in mice. Am. J. Clin. Nutr., 2009, 89, 177-184.
Mallick, A.; Bodenham, A.R. Disorders of the lymph circulation: Their relevance to anaesthesia and intensive care. Br. J. Anaesth., 2003, 91(2), 265-272.
Herrera, E.; Barbas, C.; Vitamin, E. Action, metabolism and perspectives. J. Physiol. Biochem., 2001, 57, 43-56.
Harvey, R.A.; Ferrier, D.R. Lippincott’s Illustrated Reviews: Biochemistry, 5th ed; Lippincott Williams & Wilkins: Philadelphia, Pennsylvania, 2011.
Hosomi, A.; Arita, M.; Sato, Y.; Kiyose, C.; Ueda, T.; Igarashi, O.; Arai, H.; Inoue, K. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett., 1997, 409, 105-108.
Kuhlenkamp, J.; Ronk, M.; Yusin, M.; Stolz, A.; Kaplowitz, N. Identification and purification of a human liver cytosolic tocopherol binding protein. Protein Expr. Purif., 1993, 4(5), 382-389.
Zimmer, S.; Stocker, A.; Sarbolouki, M.N.; Spycher, S.E.; Sassoon, J.; Azzi, A. A novel human tocopherol-associated protein: Cloning, in vitro expression, and characterization. J. Biol. Chem., 2000, 275(33), 25672-25680.
Mezzetti, A.; Zuliani, G.; Romano, F.; Costantini, F.; Pierdomenico, S.D.; Cuccurullo, F.; Fellin, R. Vitamin E and lipid peroxide plasma levels predict the risk of cardiovascular events in a group of healthy very old people. J. Am. Geriatr. Soc., 2001, 49(5), 533-537.
Costacou, T.; Zgibor, J.C.; Evans, R.W.; Tyurina, Y.Y.; Kagan, V.E.; Orchard, T.J. Antioxidants and coronary artery disease among individuals with type 1 diabetes: Findings from the Pittsburgh Epidemiology of Diabetes Complications Study. J. Diabetes Complications, 2006, 20(6), 387-394.
Loffredo, L.; Perri, L.; Di Castelnuovo, A.; Iacoviello, L.; De Gaetano, G.; Violi, F. Supplementation with vitamin E alone is associated with reduced myocardial infarction: A meta-analysis. Nutr. Metab. Cardiovasc. Dis., 2015, 25(4), 354-363.
Sethi, R.; Takeda, N.; Nagano, M.; Dhalla, N.S. Beneficial effects of vitamin E treatment in acute myocardial infarction. J. Cardiovasc. Pharmacol. Ther., 2000, 5, 51-58.
Saleh, N.K.; Saleh, H.A. Protective effects of vitamin E against myocardial ischemia/reperfusion injury in rats. Saudi Med. J., 2010, 31(2), 142-147.
Upaganlawar, A.; Gandhi, H.; Balaraman, R. Effect of vitamin E alone and in combination with lycopene on biochemical and histopathological alterations in isoproterenol-induced myocardial infarction in rats. J. Pharmacol. Pharmacother., 2010, 1, 24-31.
Ithayarasi, A.P.; Devi, C.S. Effect of alpha-tocopherol on lipid peroxidation in isoproterenol induced myocardial infarction in rats. Indian J. Physiol. Pharmacol., 1997, 41(4), 369-376.
Lúcio, M.; Nunes, C.; Gaspar, D.; Ferreira, H.; Lima, J.L.F.C.; Reis, S. Antioxidant activity of vitamin E and trolox: Understanding of the factors that govern lipid peroxidation studies in vitro. Food Biophys., 2009, 4(4), 312-320.
Packer, L.; Weber, S.U.; Rimbach, G. Molecular aspects of α-Tocotrienol antioxidant action and cell signalling. J. Nutr., 2001, 131(2), 369S-373S.
Scarpa, M.; Rigo, A.; Maiorino, M.; Ursini, F.; Gregolin, C. Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study. Biochim. Biophys. Acta, 1984, 801(2), 215-219.
Goh, S.H.; Hew, N.F.; Ong, A.S.H.; Choo, Y.M.; Brumby, S. Tocotrienols from palm oil: Electron spin resonance spectra of tocotrienoxyl radicals. J. Am. Oil Chem. Soc., 1990, 67(4), 250-254.
Bardhan, J.; Chatterjee, A.; Das, S.; Bandyopadhyay, S.K.; Chakraborty, R.; Raychaudhuri, U. Evaluation of cardioprotective effect of tocotrienol rich fraction from rice bran oil. Int. J. Pharm. Sci. Rev. Res., 2015, 30, 143-149.
Huwait, E.A.; Al-Ghamdi, M.A. Protective role of carnitine synergized with vitamin E against isoproterenol induced cardiac infarction in rats. Afr. J. Tradit. Complement. Altern. Med., 2017, 14(2), 25-32.
Wei, J.; Bhattacharyya, S.; Jain, M.; Varga, J. Regulation of matrix remodeling by peroxisome proliferator-activated receptor-gamma: A novel link between metabolism and fibrogenesis. Open Rheumatol. J., 2012, 6, 103-115.
Yoo, H.Y.; Chang, M.S.; Rho, H.M. Induction of the rat Cu/Zn superoxide dismutase gene through the peroxisome proliferator-responsive element by arachidonic acid. Gene, 1999, 234, 87-91.
Inoue, I.; Goto, S.; Matsunaga, T.; Nakajima, T.; Awata, T.; Hokari, S.; Komoda, T.; Katayama, S. The ligands/activators for peroxisome proliferator-activated receptor alpha (PPAR-α) and PPAR-γ increase Cu2+/Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells. Metabolism, 2001, 50, 3-11.
Girnun, G.D.; Domann, F.E.; Moore, S.A.; Robbins, M.E.C. Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter. Mol. Endocrinol., 2002, 16(12), 2793-2801.
Wayman, N.S.; Hattori, Y.; McDonald, M.C.; Mota-Filipe, H.; Cuzzocrea, S.; Pisano, B.; Chatterjee, P.K.; Thiemermann, C. Ligands of the peroxisome proliferator-activated receptors (PPAR-γ and PPAR-α) reduce myocardial infarct size. FASEB J., 2002, 16(9), 1027-1040.
Campbell, S.E.; Stone, W.L.; Whaley, S.G.; Qui, M.; Krishnan, K. Gamma (γ) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (γ) expression in SW 480 human colon cancer cell lines. BMC Cancer, 2003, 3, 25.
Fang, F.; Kang, Z.; Wong, C. Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome proliferator-activated receptors. Mol. Nutr. Food Res., 2010, 54(3), 345-352.
Yoder, B.A.; Albertine, K.H. Inflammation and lung disease in the neonatal period. Neoreviews, 2008, 9(10), e447-e457.
Huey, K.A.; Fiscus, G.; Richwine, A.F.; Johnson, R.W.; Meador, B.M. In vivo vitamin E administration attenuates interleukin-6 and interleukin-1β responses to an acute inflammatory insult in mouse skeletal and cardiac muscle. Exp. Physiol., 2008, 93(12), 1263-1272.
Nakamura, Y.K.; Omaye, S.T. Alpha-tocopherol modulates human umbilical vein endothelial cell expression of Cu/Zn superoxide dismutase and catalase and lipid peroxidation. Nutr. Res., 2008, 28(10), 671-680.
Zhong, H.; May, M.J.; Jimi, E.; Ghosh, S. The phosphorylation status of nuclear NF-κB determines its association with CBP/P300 or HDAC-1. Mol. Cell, 2002, 9(3), 625-636.
Cao, S.; Zhang, X.; Edwards, J.P.; Mosser, D.M. NF-κB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. J. Biol. Chem., 2006, 281(36), 26041-26050.
Li, L.; Wu, Z.; Li, E.; Zhang, L.; Li, L. Protective mechanism of A20 protein overexpression in acute myocardial infarction rats. West Indian Med. J., 2017, 66(6), 690-696.
Wang, Y.; Park, N-Y.; Jang, Y.; Ma, A.; Jiang, Q. Vitamin E γ-tocotrienol inhibits cytokine-stimulated NF-κB activation by induction of anti-inflammatory A20 via stress adaptive response due to modulation of sphingolipids. J. Immunol., 2015, 195, 126-133.
Dworski, R.; Han, W.; Blackwell, T.S.; Hoskins, A.; Freeman, M.L. Vitamin E prevents NRF2-suppression by allergen in asthmatic alveolar macrophages in vivo. Free Radic. Biol. Med., 2011, 51(2), 516-521.
Bozaykut, P.; Karademir, B.; Yazgan, B.; Sozen, E.; Siow, R.C.M.; Mann, G.E.; Ozer, N.K. Effects of vitamin E on peroxisome proliferator-activated receptor γ and nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced atherosclerosis. Free Radic. Biol. Med., 2014, 70, 174-181.
Zhang, B.; Tanaka, J.; Yang, L.; Yang, L.; Sakanaka, M.; Hata, R.; Maeda, N.; Mitsuda, N. Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1. Neuroscience, 2004, 126(2), 433-440.
Vassilopoulos, A.; Papazafiri, P. Attenuation of oxidative stress in HL-1 cardiomyocytes improves mitochondrial function and stabilizes HIF-1α. Free Radic. Res., 2005, 39(12), 1273-1284.
Kim, S-Y.; Kim, S-J.; Kim, B-J.; Rah, S-Y.; Chung, S.M. Im, M.-J.; Kim, U.-H. Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes. Exp. Mol. Med., 2006, 38(5), 535-545.
Nandave, M.; Mohanty, I.; Nag, T.C.; Ojha, S.K.; Mittal, R.; Kumari, S.; Arya, D.S. Cardioprotective response to chronic administration of vitamin E in isoproterenol induced myocardial necrosis: Hemodynamic, biochemical and ultrastructural studies. Indian J. Clin. Biochem., 2007, 22, 22-28.
Hu, X-X.; Fu, L.; Li, Y.; Lin, Z-B.; Liu, X.; Wang, J-F.; Chen, Y-X.; Wang, Z-P.; Zhang, X.; Ou, Z-J.; Ou, J.S. The cardioprotective effect of vitamin E (alpha-tocopherol) is strongly related to age and gender in mice. PLoS One, 2015, 10(9) e0137405

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 24 September, 2019
Page: [1407 - 1426]
Pages: 20
DOI: 10.2174/1389557519666190130164334
Price: $65

Article Metrics

PDF: 25