Open Access

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

  • Published online on: March 22, 2022     https://doi.org/10.3892/etm.2022.11272
  • Article Number: 342
  • Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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May-2022
Volume 23 Issue 5

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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