(3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one attenuates cardiac dysfunction via the apelin/APJ signaling pathway

  • Authors:
    • Mei Ding
    • Lianyue Guan
    • Chunmei Zhang
    • Ping Yang
    • Hailing Yang
  • View Affiliations

  • Published online on: April 3, 2019     https://doi.org/10.3892/mmr.2019.10122
  • Pages: 5007-5014
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Abstract

Myocardial infarction (MI) is associated with a high risk of mortality and is a major global health concern. The present study aimed to investigate the protective effects of (3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one (TIM) against MI induced by isoproterenol (ISO) in a rat model and the underlying mechanisms. Wistar rats were assigned to 4 groups (n=10): The control group received saline treatment; the ISO group received an intraperitoneal injection of ISO (100 mg/kg); and the TIM (low) and TIM (high) groups received an intraperitoneal injection of ISO, plus a 1 and 2 mg/kg dose of TIM orally, respectively. TIM rats were treated with TIM daily for 12 days and received ISO injections on the final 2 days to induce MI. Cardiac function, apoptosis index and protein expression were subsequently determined. The levels of oxidative stress markers were determined by ELISAs, whereas DNA damage was detected using a Cell Death Detection ELISA kit. Gene and protein expression were determined via reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. Following treatment with ISO, the maximum left ventricular contraction/relaxation velocity and left ventricular systolic pressure were significantly decreased, whereas the left ventricular end‑diastolic pressure was increased; however, treatment with TIM significantly ameliorated ISO‑induced cardiac dysfunction. Additionally, TIM treatment significantly decreased oxidative stress and inhibited the apoptosis of cardiomyocytes, as determined by a decrease in caspase activities, increased expression of B‑cell lymphoma 2 (Bcl‑2) and reduced expression of cleaved caspase‑3, cleaved caspase‑9 and Bcl‑2‑associated X. Furthermore, treatment with TIM upregulated the levels of apelin in the plasma and myocardium of ISO‑treated rats. The results indicated that TIM protected cardiomyocytes against ISO‑induced MI, potentially via the apelin/apelin receptor signaling pathway. The results of the present study suggested that TIM may be a potential novel therapy for the treatment of MI.

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Copy and paste a formatted citation
APA
Ding, M., Guan, L., Zhang, C., Yang, P., & Yang, H. (2019). (3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one attenuates cardiac dysfunction via the apelin/APJ signaling pathway. Molecular Medicine Reports, 19, 5007-5014. https://doi.org/10.3892/mmr.2019.10122
MLA
Ding, M., Guan, L., Zhang, C., Yang, P., Yang, H."(3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one attenuates cardiac dysfunction via the apelin/APJ signaling pathway". Molecular Medicine Reports 19.6 (2019): 5007-5014.
Chicago
Ding, M., Guan, L., Zhang, C., Yang, P., Yang, H."(3R)‑5,6,7‑trihydroxy‑3‑isopropyl‑3‑methylisochroman‑1‑one attenuates cardiac dysfunction via the apelin/APJ signaling pathway". Molecular Medicine Reports 19, no. 6 (2019): 5007-5014. https://doi.org/10.3892/mmr.2019.10122