Attenuation of neointima hyperplasia without thrombosis by a small molecule inhibitor of the store-operated channels in rabbits

WANG Tengfei; YANG Liang; LI Jing; YU Yan; CAI Xiangyu; WANG Youjun; ZHENG Xi-long; GILL Donald L.; TANG Xiang D.

Chinese︱Feedback︱Save this page

Attenuation of neointima hyperplasia without thrombosis by a small molecule inhibitor of the store-operated channels in rabbits

WANG Tengfei 1,YANG Liang 2,LI Jing 3,YU Yan 3,CAI Xiangyu 3,WANG Youjun 3,ZHENG Xi-long 4,GILL Donald L. 5,TANG Xiang D. 4 * #

1.Department of Pharmacology, Nankai University School of Medicine, TianJin 300071

2. Department of Medicine, Tianjin Chest Hospital, Tianjin 300071

3.Department of Pharmacology, Nankai University School of Medicine, Tianjin 300071

4.Department of Biochemistry and Cardiovascular Research Center,Philadelphia, PA 19104, USA

5.Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, The University of Calgary, Alberta, Canada T2N 4N1

*Correspondence author

#Submitted by

Subject:

Funding: MOE Doctorial Training Funds （No.200800550036）, NSFC grants （No.30871011 and 81072629）, Tianjin Science and Technology Support Project （No.08ZCKFSH04500）, Tianjin Natural Science Foundation （No.10JCYBJC14800）, Project “973” grant（No.2010CB945001）

Opened online:15 February 2012

Accepted by: none

Citation: WANG Tengfei,YANG Liang,LI Jing.Attenuation of neointima hyperplasia without thrombosis by a small molecule inhibitor of the store-operated channels in rabbits[OL]. [15 February 2012] http://en.paper.edu.cn/en_releasepaper/content/4463251

Objective: Stromal interacting molecule 1 (STIM1) is associated with neointima hyperplasia by mediating store-operated Ca2+ entry (SOCE) in multiple cell types. We tested whether the small molecule SOCE inhibitor could prevent neointima formation and vascular stenosis using 2-aminoethyl diphenylborate (2-APB) as a prototype drug. Methods: VSMCs were isolated from rat aortas or rabbit common carotid arteries using the tissue explant protocol and phenotypic modulation was induced by 5% fetal bovine serum (FBS). VSMC proliferation was determined using the propidium iodine/ bromodeoxyuridine double-staining method. Neointimal hyperplasia was induced in rabbit carotid arteries by air-drying injury, and 2-APB was dissolved in PLF-127 gel and coated to the extravascular surface with rapamycin as a vis-à-vis control. Results: SOCE in the VSMCs was inhibited by 2-APB accompanied by cell cycle arrest in the G1 phase. In air drying-induced rabbit carotid artery injury models, extravascular application of 2-APB effectively blunted neointima formation with a potency comparable to rapamycin. 2-APB also attenuated leukocyte infiltration by perturbing the degranulation process preserving integrity of the internal and external elastic lamina. Likewise, the SOCE inhibitor prevented platelet activation but very likely in part by an indirect mechanism involving leukocyte inactivation. More interestingly, 2-APB did not seem to induce thrombosis, a fetal complication of public concern with the use of sirolimus-eluting stents. Conclusion: Small molecule SOCE inhibitors like 2-APB could blunt neointima hyperplasia without inducing thrombosis, and thus may serve as potentially new therapeutic agents for the prevention of restenosis and proliferative vascular disorders including hypertension, coronary heart disease and diabetes. (Corresponding authors: stang@ nankai.edu.cn or stellarli@ nankai .edu.cn)

Keywords:molecular pharmacology; vascular smooth muscle cells; neointima; polymorphonuclear leukocytes (PMN); 2-aminoethyl diphenylborate (2-APB)

For this paper

● PDF (0B)
● Revision 0 　　
● Print this paper
● Recommend this paper to a friend
● Add to my favorite list

Saved Papers

Please enter a name for this paper to be shown in your personalized Saved Papers list

Tags

Add yours

Related Papers

Statistics

PDF Downloaded	262
Bookmarked	0
Recommend	6
Comments	Array

Submit your papers

Alert Name:
Alerting to:
Authentication email will be sent to your email address in 24 hours
Frequency:
Email Message Format:	Plain text Graphical(HTML)

Complete the form below and we will recommend the selected titles to your friends on your behalf. * Indicates a required field.
Your name*:
Your email address*:
Recipient's name*:
Recipient's email address*:
(multiple recipient's names and email addresses should be separated with semicolons)
Your comments:	I thought you would find the page(s) useful.

Your name:
Your email address:
Recipient's name:
Recipient's email address:
(multiple recipient's names and email addresses should be separated with semicolons)
Your comments:	I thought you would find this page useful.

Disclaimer: This message was sent to your friend using the "Send it to a friend" facility on the Sciencepaper Online’ WWW site, http://www.paper.edu.cn/en. The Sciencepaper Online is not responsible for the content of this email, and anything said in this email does not necessarily reflect the Sciencepaper Online's views.

	Check out RSS, or use RSS reader to subscribe this item

Saved Papers