Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jun 26, 2015; 7(6): 306-310
Published online Jun 26, 2015. doi: 10.4330/wjc.v7.i6.306
Perspective of future drugs targeting sterile 20/SPS1-related proline/alanine-rich kinase for blood pressure control
Gen-Min Lin, Pang-Yen Liu, Ching-Fen Wu, Wen-Been Wang, Chih-Lu Han
Gen-Min Lin, Department of Medicine, Hualien Armed Forces General Hospital, Hualien 971, Taiwan
Pang-Yen Liu, Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 104, Taiwan
Ching-Fen Wu, Department of Internal Medicine, Mennorite Christian Hospital, Hualien 970, Taiwan
Wen-Been Wang, Department of Medicine, Tri-Service General Hospital-Song Shan Branch 105, Taiwan
Chih-Lu Han, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
Author contributions: Lin GM had substantial contributions to conception and design of the study, acquisition of data, and interpretation of data; Lin GM drafted the article and all authors make critical revisions related to important intellectual content of the manuscript; all authors make final approval of the version of the article to be published.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gen-Min Lin, MD, Department of Medicine, Hualien Armed Forces General Hospital, No.163, Jiali Rd., Xincheng Township, Hualien County 97144, Hualien 971, Taiwan. farmer507@yahoo.com.tw
Telephone: +886-3-8260601 Fax: +886-3-8261370
Received: October 19, 2014
Peer-review started: October 22, 2014
First decision: February 7, 2015
Revised: March 6, 2015
Accepted: April 1, 2015
Article in press: April 7, 2015
Published online: June 26, 2015
Processing time: 249 Days and 0 Hours
Abstract

According to a genome-wide association study, intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes, mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge, phosphorylation of upstream with-no-lysine (K) (WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3 - Cullin 3 E3 ligase, hyperinsulinemia, and low potassium intake to mediate hypertension have been identified. In addition, the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010, two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently, two novel SPAK inhibitors for mice, Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK (gene or kinase).

Keywords: With-no-lysine (K) kinase; Oxidative stress-responsive kinase 1/SPS1-related proline/alanine-rich kinase kinase; Na-Cl co-transporter; Na+-K+-2Cl(-) cotransporter; Hypertension

Core tip: According to a genome-wide association study, intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase (SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. Based on current studies, targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore, we raised some viewpoints regarding the issue for antihypertensive therapy on the SPAK (gene or kinase).