Yeungnam Univ J Med.  2017 Jun;34(1):43-54. 10.12701/yujm.2017.34.1.43.

Sulfatase 1 mediates the inhibitory effect of angiotensin II type 2 receptor inhibitor on angiotensin II-induced hypertensive mediator expression and proliferation in vascular smooth muscle cells from spontaneously hypertensive rats

• Kim HY
• Cha HJ
• Kim HS

• KMID: 2400328
• DOI: http://doi.org/10.12701/yujm.2017.34.1.43

Abstract

BACKGROUND
Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR).
METHODS
Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [³ H]-thymidine incorporation.
RESULTS
Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor (ATâ‚‚ R) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of ATâ‚‚ R inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of ATâ‚‚ R mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the ATâ‚‚ R pathway was mediated by Sulf1 in SHR VSMCs.
CONCLUSION
These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the ATâ‚‚ R pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.

Keyword

Sulfatases; Angiotensin II type 2 receptor; Hypertension

MeSH Terms

Angiotensin II*
Angiotensins*
Arachidonate 12-Lipoxygenase
Blotting, Western
Down-Regulation
Endothelin-1
Heparan Sulfate Proteoglycans
Hypertension
Muscle, Smooth, Vascular*
Rats, Inbred SHR*
Real-Time Polymerase Chain Reaction
Receptor, Angiotensin, Type 2*
RNA, Messenger
Sulfatases
Angiotensin II
Angiotensins
Arachidonate 12-Lipoxygenase
Endothelin-1
Heparan Sulfate Proteoglycans
RNA, Messenger
Receptor, Angiotensin, Type 2
Sulfatases