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Correction published on 27 March 2014, see Int. J. Mol. Sci. 2014, 15(4), 5410-5411.

Open AccessReview
Int. J. Mol. Sci. 2013, 14(9), 18899-18924; doi:10.3390/ijms140918899

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

1
Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand
2
Division of Brain Science, Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
3
Department of Neurosurgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
4
Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
5
Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
6
Laboratory of Diagnostic Imaging, Department of Veterinary Science, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
7
Laboratory of Functional Foods, Department of Biomedical Engineering Osaka Institute of Technology, 5-16-1 Omiya, Asahi Ward, Osaka 535-8585, Japan
*
Author to whom correspondence should be addressed.
Received: 15 August 2013 / Revised: 7 September 2013 / Accepted: 9 September 2013 / Published: 13 September 2013
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
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Abstract

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.
Keywords: stroke; telmisartan; irbesartan; candesartan; high mobility group box 1; receptor for advanced glycation end-products stroke; telmisartan; irbesartan; candesartan; high mobility group box 1; receptor for advanced glycation end-products
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Kikuchi, K.; Tancharoen, S.; Ito, T.; Morimoto-Yamashita, Y.; Miura, N.; Kawahara, K.-I.; Maruyama, I.; Murai, Y.; Tanaka, E. Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke. Int. J. Mol. Sci. 2013, 14, 18899-18924.

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