Salt-inducible kinase 1 influences Na+,K+-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure.

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OBJECTIVES: Essential hypertension is a complex condition whose cause involves the interaction of multiple genetic and environmental factors such as salt intake. Salt-inducible kinase 1 (SIK1) is a sucrose-nonfermenting-like kinase isoform that belongs to the AMPK (5' adenosine monophosphate-activated protein kinase) family. SIK1 activity is increased by high salt intake and plays an essential role in regulating the plasma membrane Na,K-ATPase. The objective of this study was to examine whether SIK1 is present in vascular smooth muscle cells (VSMCs) and endothelial cells, whether it affects VSMC Na,K-ATPase activity and whether human SIK1 (hSIK1) represents a potential candidate for blood pressure regulation. METHODS: Localization of SIK1 was performed using immunohistochemistry, mRNA and western blot. Functional assays (Na,K-ATPase activity) were performed in VSMCs derived from rat aorta. Genotype-phenotype association studies were performed in three Swedish and one Japanese population-based cohorts. RESULTS: SIK1 was localized in human VSMCs and endothelial cells, as well as a cell line derived from rat aorta. A nonsynonymous single nucleotide polymorphism in the hSIK1 gene exon 3 (C→T, rs3746951) results in the amino acid change Gly→Ser in the SIK1 protein. SIK1-Ser was found to increase plasma membrane Na,K-ATPase activity in cultured VSMC line from rat aorta. Genotype-phenotype association studies in three Swedish and one Japanese population-based cohorts suggested that T allele (coding for Ser) was associated with lower blood pressure (P = 0.005 for SBP and P = 0.002 for DBP) and with a decrease in left ventricular mass (P = 0.048). CONCLUSION: The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.


  • Sergej Popov
  • Angela Silveira
  • Dick Wågsäter
  • Hiroshi Takemori
  • Ryousuke Oguro
  • Sachiko Matsumoto
  • Ken Sugimoto
  • Kei Kamide
  • Takuo Hirose
  • Michihiro Satoh
  • Hirohito Metoki
  • Masahiro Kikuya
  • Takayoshi Ohkubo
  • Tomohiro Katsuya
  • Hiromi Rakugi
  • Yutaka Imai
  • Fabio Sanchez
  • Ann-Christine Syvänen
  • Anders Hamsten
  • Alejandro M Bertorello
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
Sidor (från-till)2395-2403
TidskriftJournal of Hypertension
Utgåva nummer12
StatusPublished - 2011
Peer review utfördJa