Salt-inducible kinase 1 influences Na+,K+-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure
2011 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 29, no 12, 2395-2403 p.Article in journal (Refereed) Published
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.
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.
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 (15)Gly→Ser in the SIK1 protein. SIK1-(15)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 (15)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).
The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2011. Vol. 29, no 12, 2395-2403 p.
hypertension; Na+, K+-ATPase; salt sensitivity; vascular tonus
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-100331DOI: 10.1097/HJH.0b013e32834d3d55ISI: 000296914000015PubMedID: 22045124OAI: oai:DiVA.org:liu-100331DiVA: diva2:661715