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Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway

  • Authors:
    • Chao Wen
    • Fu-Shan Xue
    • Yu-Hui Wang
    • Jin-Hua Jin
    • Xu Liao
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China, Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, P.R. China
    Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 342
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    Published online on: March 22, 2022
       https://doi.org/10.3892/etm.2022.11272
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Abstract

The present study aimed to evaluate the effects of hypercholesterolemia on cardioprotection of ischemic preconditioning and α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning and explore the potential mechanisms that hypercholesterolemia affected their cardioprotection. Hypercholesterolemic and normal rats were divided into the four groups that received the following treatments: i) Hypercholesterolemic control and normal control groups; ii) hypercholesterolemic ischemia/reperfusion (HI) and normal ischemia/reperfusion (NI) groups; iii) hypercholesterolemic ischemic preconditioning (HIPC) and normal ischemic preconditioning (NIPC) groups; and iv) hypercholesterolemic PNU282987 postconditioning (HPNU) and normal PNU282987 postconditioning (NPNU) groups. Serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF‑α) and interleukin‑6 (IL‑6) levels after ischemia/reperfusion were assayed. Furthermore, infarct size and expression levels of Akt, phosphorylated (p)‑Akt and endothelial nitric oxide synthase (eNOS) in ischemic myocardium were assessed. Compared with the NI group, serum LDH, CK‑MB, cTnI, TNF‑α and IL‑6 levels and infarct size were significantly decreased, and myocardial p‑Akt/Akt and eNOS/GAPDH ratios were significantly increased in the NIPC and NPNU groups. Compared with the HI group, serum CK‑MB, cTnI, TNF‑α and IL‑6 levels and infarct size were significantly decreased in the HIPC group; however, myocardial p‑Akt/Akt and eNOS/GAPDH ratios did not significantly change in the HIPC group. Furthermore, there were no significant difference between the HI and HPNU groups in serum LDH, CK‑MB, cTnI, TNF‑α and IL‑6 levels, infarct size, myocardial p‑Akt/Akt and eNOS/GAPDH ratios. In conclusion, hypercholesterolemia could aggravate myocardial ischemia/reperfusion injury, attenuate cardioprotection of ischemic preconditioning and eliminate cardioprotection from α7nAChR agonist postconditioning by enhancing inflammation and inhibiting PI3K/Akt/eNOS pathway.
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1 

Rossello X, Lobo-Gonzalez M and Ibanez B: Editor's choice-pathophysiology and therapy of myocardial ischaemia/reperfusion syndrome. Eur Heart J Acute Cardiovasc Care. 8:443–456. 2019.PubMed/NCBI View Article : Google Scholar

2 

Hausenloy DJ and Yellon DM: Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol. 13:193–209. 2016.PubMed/NCBI View Article : Google Scholar

3 

Wu Y, Liu H and Wang X: Cardioprotection of pharmacological postconditioning on myocardial ischemia/reperfusion injury. Life Sci. 264(118628)2021.PubMed/NCBI View Article : Google Scholar

4 

Xiong J, Yuan YJ, Xue FS, Wang Q, Cheng Y, Li RP, Liao X and Liu JH: Postconditioning with α7nAChR agonist attenuates systemic inflammatory response to myocardial ischemia-reperfusion injury in rats. Inflammation. 35:1357–1364. 2012.PubMed/NCBI View Article : Google Scholar

5 

Sack MN and Murphy E: The role of comorbidities in cardioprotection. J Cardiovasc Pharmacol Ther. 16:267–272. 2011.PubMed/NCBI View Article : Google Scholar

6 

Andreadou I, Schulz R, Badimon L, Adameová A, Kleinbongard P, Lecour S, Nikolaou PE, Falcão-Pires I, Vilahur G, Woudberg N, et al: Hyperlipidaemia and cardioprotection: Animal models for translational studies. Br J Pharmacol. 177:5287–5311. 2020.PubMed/NCBI View Article : Google Scholar

7 

Bøtker HE: The future of cardioprotection-pointing toward patients at elevated risk as the target populations. J Cardiovasc Pharmacol Ther. 25:487–493. 2020.PubMed/NCBI View Article : Google Scholar

8 

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 cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol. 174:1555–1569. 2017.PubMed/NCBI View Article : Google Scholar

9 

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.PubMed/NCBI View Article : Google Scholar

10 

Ueda Y, Kitakaze M, Komamura K, Minamino T, Asanuma H, Sato H, Kuzuya T, Takeda H and Hori M: Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction. J Am Coll Cardiol. 34:2120–2125. 1999.PubMed/NCBI View Article : Google Scholar

11 

Tang XL, Takano H, Xuan YT, Sato H, Kodani E, Dawn B, Zhu Y, Shirk G, Wu WJ and Bolli R: Hypercholesterolemia abrogates late preconditioning via a tetrahydrobiopterin-dependent mechanism in conscious rabbits. Circulation. 112:2149–2156. 2005.PubMed/NCBI View Article : Google Scholar

12 

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 hypercholesterolemic and normal anesthetized rabbits. Atherosclerosis. 188:356–362. 2006.PubMed/NCBI View Article : Google Scholar

13 

Jung O, Jung W, Malinski T, Wiemer G, Schoelkens BA and Linz W: Ischemic preconditioning and infarct mass: The effect of hypercholesterolemia and endothelial dysfunction. Clin Exp Hypertens. 22:165–179. 2000.PubMed/NCBI View Article : Google Scholar

14 

Yang JT, Wang J, Zhou XR, Xiao C, Lou YY, Tang LH, Zhang FJ and Qian LB: Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling. Naunyn Schmiedebergs Arch Pharmacol. 391:719–728. 2018.PubMed/NCBI View Article : Google Scholar

15 

Zhang JQ, Wang Q, Xue FS, Li RP, Cheng Y, Cui XL, Liao X and Meng FM: Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury. Chin Med J (Engl). 126:3949–3955. 2013.PubMed/NCBI

16 

Low LD, Lu L, Chan CY, Chen J, Yang HH, Yu H, Lee CGL, Ng KH and Yap HK: IL-13-driven alterations in hepatic cholesterol handling contributes to hypercholesterolemia in a rat model of minimal change disease. Clin Sci (Lond). 134:225–237. 2020.PubMed/NCBI View Article : Google Scholar

17 

He JY, Fan SX, Ma YL, Cao XF, Tian T and Liu Y: Hypercholesterolemia abolishes the protective effect of ischemic preconditioning on myocardial ischemia-reperfusion injury in rats via PI3K/Akt pathway. Chin Rem Clin. 19:4024–4027. 2019.

18 

Cui X, Wang S, Xue F, Yang G, Li H, Liu Y and Liao X: Mechanism underlying inhibition of inflammatory responses induced by α7nAChR agonist postconditioning alone or in combination with remote limb ischemic postconditioning during myocardial I/R in rats: The relationship with GSK-3β (Chinese). Chin J Anesthesiol. 38:78–82. 2018.

19 

Ungi I, Ungi T, Ruzsa Z, Nagy E, Zimmermann Z, Csont T and Ferdinandy P: Hypercholesterolemia attenuates the anti-ischemic effect of preconditioning during coronary angioplasty. Chest. 128:1623–1628. 2005.PubMed/NCBI View Article : Google Scholar

20 

Kocić I, Konstański Z, Kaminski M, Dworakowska D and Dworakowski R: Experimental hyperlipidemia prevents the protective effect of ischemic preconditioning on the contractility and responsiveness to phenylephrine of rat-isolated stunned papillary muscle. Gen Pharmacol. 33:213–219. 1999.PubMed/NCBI View Article : Google Scholar

21 

Vincent A, Lattuca B, Merlet N, Sportouch-Dukhan C and Barrère-Lemaire S: New insights in research about acute ischemic myocardial injury and inflammation. Antiinflamm Antiallergy Agents Med Chem. 12:47–54. 2013.PubMed/NCBI View Article : Google Scholar

22 

Steffens S, Montecucco F and Mach F: The inflammatory response as a target to reduce myocardial ischaemia and reperfusion injury. Thromb Haemost. 102:240–247. 2009.PubMed/NCBI View Article : Google Scholar

23 

Rosenberg JH, Werner JH, Moulton MJ and Agrawal DK: Current modalities and mechanisms underlying cardioprotection by ischemic conditioning. J Cardiovasc Transl Res. 11:292–307. 2018.PubMed/NCBI View Article : Google Scholar

24 

Hausenloy DJ and Yellon DM: Reperfusion injury salvage kinase signalling: Taking a RISK for cardioprotection. Heart Fail Rev. 12:217–234. 2007.PubMed/NCBI View Article : Google Scholar

25 

He X, Zhao M, Bi XY, Yu XJ and Zang WJ: Delayed preconditioning prevents ischemia/reperfusion-induced endothelial injury in rats: Role of ROS and eNOS. Lab Invest. 93:168–180. 2013.PubMed/NCBI View Article : Google Scholar

26 

Sun Y, Jiang C, Jiang J and Qiu L: Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway. Clin Exp Pharmacol Physiol. 44:946–953. 2017.PubMed/NCBI View Article : Google Scholar

27 

Bai J, Wang Q, Qi J, Yu H, Wang C, Wang X, Ren Y and Yang F: Promoting effect of baicalin on nitric oxide production in CMECs via activating the PI3K-AKT-eNOS pathway attenuates myocardial ischemia-reperfusion injury. Phytomedicine. 63(153035)2019.PubMed/NCBI View Article : Google Scholar

28 

Jones SP, Girod WG, Palazzo AJ, Granger DN, Grisham MB, Jourd'Heuil D, Huang PL and Lefer DJ: Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase. Am J Physiol. 276:H1567–H1573. 1999.PubMed/NCBI View Article : Google Scholar

29 

Shah DI and Singh M: Possible role of Akt to improve vascular endothelial dysfunction in diabetic and hyperhomocysteinemic rats. Mol Cell Biochem. 295:65–74. 2007.PubMed/NCBI View Article : Google Scholar

30 

Genda S, Miura T, Miki T, Ichikawa Y and Shimamoto K: K(ATP) channel opening is an endogenous mechanism of protection against the no-reflow phenomenon but its function is compromised by hypercholesterolemia. J Am Coll Cardiol. 40:1339–1346. 2002.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Wen C, Xue F, Wang Y, Jin J and Liao X: Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway. Exp Ther Med 23: 342, 2022.
APA
Wen, C., Xue, F., Wang, Y., Jin, J., & Liao, X. (2022). Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway. Experimental and Therapeutic Medicine, 23, 342. https://doi.org/10.3892/etm.2022.11272
MLA
Wen, C., Xue, F., Wang, Y., Jin, J., Liao, X."Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway". Experimental and Therapeutic Medicine 23.5 (2022): 342.
Chicago
Wen, C., Xue, F., Wang, Y., Jin, J., Liao, X."Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway". Experimental and Therapeutic Medicine 23, no. 5 (2022): 342. https://doi.org/10.3892/etm.2022.11272
Copy and paste a formatted citation
x
Spandidos Publications style
Wen C, Xue F, Wang Y, Jin J and Liao X: Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway. Exp Ther Med 23: 342, 2022.
APA
Wen, C., Xue, F., Wang, Y., Jin, J., & Liao, X. (2022). Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway. Experimental and Therapeutic Medicine, 23, 342. https://doi.org/10.3892/etm.2022.11272
MLA
Wen, C., Xue, F., Wang, Y., Jin, J., Liao, X."Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway". Experimental and Therapeutic Medicine 23.5 (2022): 342.
Chicago
Wen, C., Xue, F., Wang, Y., Jin, J., Liao, X."Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway". Experimental and Therapeutic Medicine 23, no. 5 (2022): 342. https://doi.org/10.3892/etm.2022.11272
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