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Atorvastatin ameliorates the contractile dysfunction of the aorta induced by organ culture

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Abstract

Statins are widely used in the treatment of hypercholesterolemia. Studies have demonstrated that statins could maintain vascular contractile function through inhibiting the transformation of vascular smooth muscle cells (VSMCs) from the contractile phenotype to the synthetic phenotype. However, the underlying mechanisms have not been fully elucidated. The effect of atorvastatin on the thoracic aorta of Sprague-Dawley rats cultured in serum-free conditions in vitro was evaluated. Aortic constriction was induced by high potassium, phenylephrine, and CaCl2. The protein expression levels of α1 adrenoceptor; inositol 1,4,5-trisphosphate (IP3) receptor; protein kinase Cδ (PKCδ); stromal interaction molecule 1 (STIM1); high-voltage activated dihydropyridine-sensitive (L type, Cav1.2) channels; and two contractile phenotype marker proteins [α-smooth muscle actin (α-SMA) and myosin (SM-MHC)] were determined by western blotting. Compared with the fresh control, the constriction of rat aorta was impaired after culture in serum-free medium for 24 h. The impaired contraction of cultured aortas was mediated by Cav1.2 and store-operated Ca2+ (SOC) channel, which could be improved by atorvastatin at 20 μM. The protein expression levels of α1 adrenoceptor, IP3 receptor, PKCδ, STIM1, Cav1.2, α-SMA, and SM-MHC in the aortas cultured in serum-free conditions were decreased significantly. Atorvastatin partially prevented the reduction in the contractility and the downregulation of these proteins in cultured aortas. The transformation of the VSMC phenotype is associated with the vasoconstriction dysfunction of cultured aortas. Atorvastatin may protect vascular function by modulating calcium signaling pathways.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81302779, No. 81273516, No. 81470440, No. 81370295) and Guangdong Provincial Medical Science Foundation (No. A2015229).

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Author notes

  1. Feng Zhou and Fang Rao contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China

    Feng Zhou & You-Qing Deng

  2. Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China

    Fang Rao, Hui Yang, Su-Juan Kuang, Fei-Long Wu, Shu-Lin Wu, Yu-Mei Xue & Chun-Yu Deng

  3. Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, China

    Fang Rao, Hui Yang, Su-Juan Kuang, Fei-Long Wu, Shu-Lin Wu, Yu-Mei Xue & Chun-Yu Deng

  4. Provincial Key Laboratory of Clinical Pharmacology, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China

    Fang Rao, Hui Yang, Su-Juan Kuang, Fei-Long Wu, Shu-Lin Wu, Yu-Mei Xue & Chun-Yu Deng

  5. Department of Neurology, Jiangxi Provincial People’s Hospital, 92 Aiguo Road, Nanchang, 330000, People’s Republic of China

    Xiao-Mu Wu

  6. Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080, People’s Republic of China

    Chun-Yu Deng

Authors
  1. Feng Zhou
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  2. Fang Rao
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Contributions

FR, XMW, and CYD conceived and designed the research.

FZ, HY, SJK, and FLW conducted the experiments.

YQD and YMX analyzed the data.

FZ and FR wrote the manuscript.

SLW edited the manuscript.

All authors read and approved the manuscript.

Corresponding authors

Correspondence to Xiao-Mu Wu or Chun-Yu Deng.

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The authors declare that they have no conflict of interest.

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Zhou, F., Rao, F., Deng, YQ. et al. Atorvastatin ameliorates the contractile dysfunction of the aorta induced by organ culture. Naunyn-Schmiedeberg's Arch Pharmacol 392, 19–28 (2019). https://doi.org/10.1007/s00210-018-1559-4

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  • DOI: https://doi.org/10.1007/s00210-018-1559-4

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