Open Access

Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats

  • Authors:
    • Lian Duan
    • Changbin Liang
    • Xuying Li
    • Zijun Huang
    • Shuang Liu
    • Nan Wu
    • Dalin Jia
  • View Affiliations

  • Published online on: April 15, 2019     https://doi.org/10.3892/ijmm.2019.4166
  • Pages: 2451-2461
  • Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia‑reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol‑enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis‑related proteins were detected by western blotting. Overall, the results demonstrated that low‑dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose‑regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase‑3β, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase‑9 and cleaved caspase‑3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI in hypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.

References

1 

Bulluck H, Yellon DM and Hausenloy DJ: Reducing myocardial infarct size: Challenges and future opportunities. Heart. 102:341–348. 2016. View Article : Google Scholar :

2 

Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA and Vinten-Johansen J: Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 285:H579–H588. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Shinohara G, Morita K, Nagahori R, Koh Y, Kinouchi K, Abe T and Hashimoto K: Ischemic postconditioning promotes left ventricular functional recovery after cardioplegic arrest in an in vivo piglet model of global ischemia reperfusion injury on cardiopulmonary bypass. J Thorac Cardiovasc Surg. 142:926–932. 2011. View Article : Google Scholar : PubMed/NCBI

4 

You L, Li L, Xu Q, Ren J and Zhang F: Postconditioning reduces infarct size and cardiac myocyte apoptosis via the opioid receptor and JAK-STAT signaling pathway. Mol Biol Rep. 38:437–443. 2011. View Article : Google Scholar

5 

Cao S, Liu Y, Wang H, Mao X, Chen J, Liu J, Xia Z, Zhang L, Liu X and Yu T: Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts. Peer J. 4:e17062016. View Article : Google Scholar : PubMed/NCBI

6 

Tong G, Aponte AM, Kohr MJ, Steenbergen C, Murphy E and Sun J: Postconditioning leads to an increase in protein S-nitrosylation. Am J Physiol Heart Circ Physiol. 306:H825–H832. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Araszkiewicz A, Grygier M, Pyda M, Rajewska J, Michalak M, Lesiak M and Grajek S: Postconditioning reduces enzymatic infarct size and improves microvascular reperfusion in patients with ST-segment elevation myocardial infarction. Cardiology. 129:250–257. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Araszkiewicz A, Grygier M, Pyda M, Rajewska J, Lesiak M and Grajek S: Postconditioning attenuates early ventricular arrhythmias in patients with high-risk ST-segment elevation myocardial infarction. J Cardiol. 65:459–465. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF and Schulz R: Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev. 66:1142–1174. 2014. View Article : Google Scholar : PubMed/NCBI

10 

D'Annunzio V, Donato M, Buchholz B, Pérez V, Miksztowicz V, Berg G and Gelpi RJ: High cholesterol diet effects on ischemia-reperfusion injury of the heart. Can J Physiol Pharmacol. 90:1185–1196. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Wu N, Zhang X, Jia P and Jia D: Hypercholesterolemia aggravates myocardial ischemia reperfusion injury via activating endoplasmic reticulum stress-mediated apoptosis. Exp Mol Pathol. 99:449–454. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Wu N, Zhang X, Guan Y, Shu W, Jia P and Jia D: Hypercholesterolemia abrogates the cardioprotection of ischemic postconditioning in isolated rat heart: Roles of glycogen synthase kinase-3β and the mitochondrial permeability transition pore. Cell Biochem Biophys. 69:123–130. 2014. View Article : Google Scholar

13 

Wu N, Zhang X, Jia P and Jia D: Hypercholesterolemia abrogates the protective effect of ischemic postconditioning by induction of apoptosis and impairment of activation of reperfusion injury salvage kinase pathway. Biochem Biophys Res Commun. 458:148–153. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Andreadou I, Iliodromitis EK, Lazou A, Görbe A, Giricz Z, Schulz R and Ferdinandy P: Effect of hypercholesterolaemia on myocardial function, ischaemia-reperfusion injury and cardio-protection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol. 174:1555–1569. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Andreadou I, Farmakis D, Prokovas E, Sigala F, Zoga A, Spyridaki K, Papalois A, Papapetropoulos A, Anastasiou-Nana M, Kremastinos DT and Iliodromitis EK: Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning: Effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress. Cardiovasc Res. 94:501–509. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Wu N, Li W, Shu W, Lv Y and Jia D: Inhibition of Rho-kinase by fasudil restores the cardioprotection of ischemic postcondi-tioninng in hypercholesterolemic rat heart. Mol Med Rep. 10:2517–2524. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Wu N, Li WN, Shu WQ, Lv Y and Jia DL: Blocking the mitochondrial permeability transition pore with cyclosporine-A can restore cardioprotection of ischemic postconditioning in hypercholesterolemic rat heart. Eur Rev Med Pharmacol Sci. 19:446–454. 2015.PubMed/NCBI

18 

Riccioni G, Mancini B, Di Ilio E, Bucciarelli T and D'Orazio N: Protective effect of lycopene in cardiovascular disease. Eur Rev Med Pharmacol Sci. 12:183–190. 2008.PubMed/NCBI

19 

Xu J, Hu H, Chen B, Yue R, Zhou Z, Liu Y, Zhang S, Xu L, Wang H and Yu Z: Lycopene protects against hypoxia/reoxygenation injury by alleviating ER stress induced apoptosis in neonatal mouse cardiomyocytes. PLoS One. 10:e01364432015. View Article : Google Scholar : PubMed/NCBI

20 

Yue R, Hu H, Yiu KH, Luo T, Zhou Z, Xu L, Zhang S, Li K and Yu Z: Lycopene protects against hypoxia/reoxygenation-induced apoptosis by preventing mitochondrial dysfunction in primary neonatal mouse cardiomyocytes. PLoS One. 7:e507782012. View Article : Google Scholar : PubMed/NCBI

21 

Kastenmayer RJ, Moore RM, Bright AL, Torres-Cruz R and Elkins WR: Select agent and toxin regulations: Beyond the eighth edition of the guide for the care and use of laboratory animals. J Am Assoc Lab Anim Sci. 51:333–338. 2012.PubMed/NCBI

22 

Jia P, Liu C, Wu N, Jia D and Sun Y: Agomelatine protects against myocardial ischemia reperfusion injury by inhibiting mitochondrial permeability transition pore opening. Am J Transl Res. 10:1310–1323. 2018.PubMed/NCBI

23 

Bayramoglu G, Bayramoglu A, Altuner Y, Uyanoglu M and Colak S: The effects of lycopene on hepatic ischemia/reperfusion injury in rats. Cytotechnology. 67:487–491. 2015. View Article : Google Scholar :

24 

Göncü T, Oğuz E, Sezen H, Koçarslan S, Oğuz H, Akal A, Adıbelli FM, Çakmak S and Aksoy N: Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats. Arq Bras Oftalmol. 79:357–362. 2016. View Article : Google Scholar

25 

Güzel M, Sönmez MF, Baştuğ O, Aras NF, Öztürk AB, Küçükaydın M and Turan C: Effectiveness of lycopene on experimental testicular torsion. J Pediatr Surg. 51:1187–1191. 2016. View Article : Google Scholar

26 

Grall S, Prunier-Mirebeau D, Tamareille S, Mateus V, Lamon D, Furber A and Prunier F: Endoplasmic reticulum stress pathway involvement in local and remote myocardial ischemic conditioning. Shock. 39:433–439. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Jia D: The protective effect of mitochondrial ATP-sensitive K+ channel opener, nicorandil, combined with Na+/Ca2+ exchange blocker KB-R7943 on myocardial ischemia-reperfusion injury in rat. Cell Biochem Biophys. 60:219–224. 2011. View Article : Google Scholar

28 

Zingarelli B, Salzman AL and Szabó C: Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res. 83:85–94. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Wu N, Zhang X and Jia D: High-dose fasudil preconditioning and postconditioning attenuate myocardial ischemia-reperfusion injury in hypercholesterolemic rats. Mol Med Rep. 9:560–566. 2014. View Article : Google Scholar

30 

Hausenloy DJ, Tsang A and Yellon DM: The reperfusion injury salvage kinase pathway: A common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med. 15:69–75. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Zhu H, Ding Y, Xu X, Li M, Fang Y, Gao B, Mao H, Tong G, Zhou L and Huang J: Prostaglandin E1 protects coronary microvascular function via the glycogen synthase kinase 3β-mitochondrial permeability transition pore pathway in rat hearts subjected to sodium laurate-induced coronary microembolization. Am J Transl Res. 9:2520–2534. 2017.

32 

Zhao JL, Yang YJ, You SJ, Cui CJ and Gao RL: Different effects of postconditioning on myocardial no-reflow in the normal and hypercholesterolemic mini-swines. Microvasc Res. 73:137–142. 2007. View Article : Google Scholar

33 

Iliodromitis EK, Zoga A, Vrettou A, Andreadou I, Paraskevaidis IA, Kaklamanis L and Kremastinos DT: The effectiveness of postconditioning and preconditioning on infarct size in hypercho-lesterolemic and normal anesthetized rabbits. Atherosclerosis. 188:356–362. 2006. View Article : Google Scholar

34 

Donato M, D'Annunzio V, Berg G, Gonzalez G, Schreier L, Morales C, Wikinski RL and Gelpi RJ: Ischemic postconditioning reduces infarct size by activation of A1 receptors and K+(ATP) channels in both normal and hypercholesterolemic rabbits. J Cardiovasc Pharmacol. 49:287–292. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Iliodromitis EK, Andreadou I, Prokovas E, Zoga A, Farmakis D, Fotopoulou T, Ioannidis K, Paraskevaidis IA and Kremastinos DT: Simvastatin in contrast to postconditioning reduces infarct size in hyperlipidemic rabbits: Possible role of oxidative/nitrosative stress attenuation. Basic Res Cardiol. 105:193–203. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Zeng YC, Hu MY, Qu SL and Zhou GY: Effects of lycopene on blood lipid and red blood cell of rat with hypercholesterolemia. Zhonghua Yu Fang Yi Xue Za Zhi. 43:1064–1068. 2009.In Chinese.

37 

Paolini M, Abdel-Rahman SZ, Sapone A, Pedulli GF, Perocco P, Cantelli-Forti G and Legator MS: Beta-carotene: A cancer chemo-preventive agent or a co-carcinogen. Mutat Res. 543:195–200. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Yeh SL and Hu ML: Induction of oxidative DNA damage in human foreskin fibroblast Hs68 cells by oxidized beta-Carotene and lycopene. Free Radic Res. 35:203–213. 2001. View Article : Google Scholar : PubMed/NCBI

39 

Rasheva VI and Domingos PM: Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis. 14:996–1007. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Szegezdi E, Logue SE, Gorman AM and Samali A: Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 7:880–885. 2006. View Article : Google Scholar : PubMed/NCBI

41 

Sivaraman V, Mudalagiri NR, Di Salvo C, Kolvekar S, Hayward M, Yap J, Keogh B, Hausenloy DJ and Yellon DM: Postconditioning protects human atrial muscle through the activation of the RISK pathway. Basic Res Cardiol. 102:453–459. 2007. View Article : Google Scholar : PubMed/NCBI

42 

Gomez L, Paillard M, Thibault H, Derumeaux G and Ovize M: Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion. Circulation. 117:2761–2768. 2008. View Article : Google Scholar : PubMed/NCBI

43 

Miki T, Miura T, Hotta H, Tanno M, Yano T, Sato T, Terashima Y, Takada A, Ishikawa S and Shimamoto K: Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phosphoglycogen synthase kinase-3beta-mediated suppression of mitochondrial permeability transition. Diabetes. 58:2863–2872. 2009. View Article : Google Scholar : PubMed/NCBI

44 

Bell RM, Mocanu MM and Yellon DM: Retrograde heart perfusion: The Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol. 50:940–950. 2011. View Article : Google Scholar : PubMed/NCBI

45 

Hu L, Cheng XW, Song H, Inoue A, Jiang H, Li X, Shi GP, Kozawa E, Okumura K and Kuzuya M: Cathepsin K activity controls injury-related vascular repair in mice. Hypertension. 63:607–615. 2014. View Article : Google Scholar :

46 

Cheng Wu H, Hu XW, Takeshita L, Hu K, Du C, Li Q, Zhu X, Huang E, Yisireyili ZM, et al: Cathepsin S activity controls injury-related vascular repair in mice via the TLR2-mediated p38MAPK and PI3K-Akt/p-HDAC6 signaling pathway. Arterioscler Thromb Vasc Biol. 36:1549–1557. 2016. View Article : Google Scholar : PubMed/NCBI

47 

Cheng XW, Shi GP, Kuzuya M, Sasaki T, Okumura K and Murohara T: Role for cysteine protease cathepsins in heart disease: Focus on biology and mechanisms with clinical implication. Circulation. 125:1551–1562. 2012. View Article : Google Scholar : PubMed/NCBI

48 

Ogasawara S, Cheng XW, Inoue A, Hu L, Piao L, Yu C, Goto H, Xu W, Zhao G, Lei Y, et al: Cathepsin K activity controls cardiotoxin-induced skeletal muscle repair in mice. J Cachexia Sarcopenia Muscle. 9:160–175. 2018. View Article : Google Scholar

49 

Cadenas S: ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic Biol Med. 117:76–89. 2018. View Article : Google Scholar : PubMed/NCBI

50 

Andrienko TN, Pasdois P, Pereira GC, Ovens MJ and Halestrap AP: The role of succinate and ROS in reperfusion injury-A critical appraisal. J Mol Cell Cardiol. 110:1–14. 2017. View Article : Google Scholar : PubMed/NCBI

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June 2019
Volume 43 Issue 6

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Copy and paste a formatted citation
APA
Duan, L., Liang, C., Li, X., Huang, Z., Liu, S., Wu, N., & Jia, D. (2019). Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats. International Journal of Molecular Medicine, 43, 2451-2461. https://doi.org/10.3892/ijmm.2019.4166
MLA
Duan, L., Liang, C., Li, X., Huang, Z., Liu, S., Wu, N., Jia, D."Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats". International Journal of Molecular Medicine 43.6 (2019): 2451-2461.
Chicago
Duan, L., Liang, C., Li, X., Huang, Z., Liu, S., Wu, N., Jia, D."Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats". International Journal of Molecular Medicine 43, no. 6 (2019): 2451-2461. https://doi.org/10.3892/ijmm.2019.4166