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Intramyocardial Delivery of HMGB1 by a Novel Thermosensitive Hydrogel Attenuates Cardiac Remodeling and Improves Cardiac Function After Myocardial Infarction

He, Yi-Yu MD*,†; Wen, Ying MD*,†; Zheng, Xiao-Xin MD*,†; Jiang, Xue-Jun MD*,†

Journal of Cardiovascular Pharmacology: April 2013 - Volume 61 - Issue 4 - p 283–290
doi: 10.1097/FJC.0b013e31827ecd50
Original Article

Background: High-mobility group box 1 (HMGB1), a nuclear protein, has been recently reported to attenuate cardiac remodeling after myocardial infarction (MI). This study was designed to investigate whether this effect could be strengthened by local intramyocardial injection of HMGB1 along with a novel Dex-PCL-HEMA/PNIPAAm hydrogel and ascertain its possible mechanism of action.

Methods: Rat models were induced by coronary artery ligation. Phosphate-buffered solution, Dex-PCL-HEMA/PNIPAAm hydrogel, HMGB1 in phosphate-buffered solution, or HMGB1 in hydrogel was injected into a peri-infarcted area of cardiac tissue immediately after MI.

Results: The injection of HMGB1 along with hydrogel improved cardiac function and reduced collagen content. Additionally, the number of c-Kit+/Ki67+, α-sarcomeric+/MEF2C+, and α-sarcomeric+/Ki67+ cells were increased significantly compared with the results of using either agent alone.

Conclusions: HMGB1 injection with Dex-PCL-HEMA/PNIPAAm hydrogel attenuates cardiac remodeling and improves cardiac function after MI by inducing myocardial regeneration.

*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China

Division of Cardiology, Cardiovascular Research Institute of Wuhan University, Wuhan, China.

Reprints: Xuejun Jiang, MD, Division of Cardiology, Cardiovascular Research Institute of Wuhan University, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan 430060, China (e-mail:

Supported by a grant from the National Natural Science Foundation of China (No.81170307) and the Fundamental Research Funds for the Central Universities.

The authors report no conflicts of interest.

Received July 16, 2012

Accepted November 16, 2012

© 2013 Lippincott Williams & Wilkins, Inc.