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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 1, pp 19–28 | Cite as

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

  • Feng Zhou
  • Fang Rao
  • You-Qing Deng
  • Hui Yang
  • Su-Juan Kuang
  • Fei-Long Wu
  • Shu-Lin Wu
  • Yu-Mei Xue
  • Xiao-Mu WuEmail author
  • Chun-Yu DengEmail author
Original Article
  • 76 Downloads

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.

Keywords

Atorvastatin Organ culture Aorta Calcium handling α1 adrenoceptor 

Notes

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).

Authors’ 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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

210_2018_1559_MOESM1_ESM.docx (101 kb)
ESM 1 (DOCX 100 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyThe Third Affiliated Hospital of Nanchang UniversityNanchangPeople’s Republic of China
  2. 2.Department of CardiologyGuangdong Cardiovascular InstituteGuangzhouChina
  3. 3.Research Center of Medical SciencesGuangdong General HospitalGuangzhouChina
  4. 4.Provincial Key Laboratory of Clinical PharmacologyGuangdong Academy of Medical SciencesGuangzhouPeople’s Republic of China
  5. 5.Department of NeurologyJiangxi Provincial People’s HospitalNanchangPeople’s Republic of China
  6. 6.Guangdong Cardiovascular Institute, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouPeople’s Republic of China

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