The TLR4 (Toll-like receptor 4) signal plays an important role in immunity in CAD (coronary artery disease). miR-146a/b (where miR is microRNA) regulates the TLR4 downstream molecules IRAK1 (interleukin-1-receptor-associated kinase 1) and TRAF6 (tumour-necrosis-factor-receptor-associated factor 6). It has also been reported that statins and RAS (renin–angiotensin system) inhibition and have anti-atherosclerotic properties. In the present study, we have investigated whether miR-146a/b was expressed with the TLR4 signal in CAD patients, and whether combined treatment with a statin and RAS inhibition might affect these levels. A total of 66 patients with CAD and 33 subjects without CAD (non-CAD) were enrolled. Patients with CAD were randomized to 12 months of combined treatment with atorvastatin and telmisartan [an ARB (angiotensin II receptor blocker)] or atorvastatin and enalapril [an ACEI (angiotensin-converting enzyme inhibitor)]. PBMCs (peripheral blood mononuclear cells) were obtained from peripheral blood at baseline and after 12 months. Levels of miR-146a/b, IRAK1 mRNA, TRAF6 mRNA and TLR4 mRNA/TLR4 protein were significantly higher in the CAD group than in the non-CAD group (all P<0.01). Levels of miR-146a/b were positively correlated with IRAK1 mRNA and TRAF6 mRNA levels. After 12 months of treatment, these levels were markedly decreased in the ARB and ACEI groups, with the decrease in the ARB group being greater than that in the ACEI group (all P<0.05). In our 12-month follow-up study, high levels of miR-146a and TLR4 mRNA/TLR4 protein at baseline were independent predictors of cardiac events. The present study demonstrates that combined treatment with an ARB and a statin decreases miR-146a/b and the TLR4 signal in CAD patients, possibly contributing to the anti-atherogenic effects of ARBs and statins in this disorder.
Skip Nav Destination
Article navigation
Research Article|
July 23 2010
Expression of miR-146a/b is associated with the Toll-like receptor 4 signal in coronary artery disease: effect of renin–angiotensin system blockade and statins on miRNA-146a/b and Toll-like receptor 4 levels
Yuji Takahashi;
Yuji Takahashi
1Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan
Search for other works by this author on:
Mamoru Satoh;
1Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan
Correspondence: Dr Mamoru Satoh (email [email protected]).
Search for other works by this author on:
Yoshitaka Minami;
Yoshitaka Minami
1Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan
Search for other works by this author on:
Tsuyoshi Tabuchi;
Tsuyoshi Tabuchi
1Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan
Search for other works by this author on:
Tomonori Itoh;
Tomonori Itoh
1Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan
Search for other works by this author on:
Motoyuki Nakamura
Motoyuki Nakamura
1Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 05 2010
Revision Received:
May 04 2010
Accepted:
June 04 2010
Accepted Manuscript online:
June 04 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 119 (9): 395–405.
Article history
Received:
January 05 2010
Revision Received:
May 04 2010
Accepted:
June 04 2010
Accepted Manuscript online:
June 04 2010
Citation
Yuji Takahashi, Mamoru Satoh, Yoshitaka Minami, Tsuyoshi Tabuchi, Tomonori Itoh, Motoyuki Nakamura; Expression of miR-146a/b is associated with the Toll-like receptor 4 signal in coronary artery disease: effect of renin–angiotensin system blockade and statins on miRNA-146a/b and Toll-like receptor 4 levels. Clin Sci (Lond) 1 October 2010; 119 (9): 395–405. doi: https://doi.org/10.1042/CS20100003
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |