Theranostics 2019; 9(7):1980-1992. doi:10.7150/thno.31073

Research Paper

Hyaluronic Acid Oligosaccharides Improve Myocardial Function Reconstruction and Angiogenesis against Myocardial Infarction by Regulation of Macrophages

Ning Wang1*, Chao Liu1*, Xinxin Wang1, Tao He1, Lu Li1, Xiuqi Liang1, Li Wang1, Linjiang Song2, Yuquan Wei1, Qinjie Wu1✉, Changyang Gong1✉

1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China
2. School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. China
*These authors contributed equally to this work.

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Citation:
Wang N, Liu C, Wang X, He T, Li L, Liang X, Wang L, Song L, Wei Y, Wu Q, Gong C. Hyaluronic Acid Oligosaccharides Improve Myocardial Function Reconstruction and Angiogenesis against Myocardial Infarction by Regulation of Macrophages. Theranostics 2019; 9(7):1980-1992. doi:10.7150/thno.31073. Available from https://www.thno.org/v09p1980.htm

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Abstract

Myocardial infarction (MI) is identified as one of the major causes of mortality and disability worldwide. For severe myocardial infarction, even advanced forms of clinical intervention often lead to unsatisfactory therapeutic results. Thus, alternative strategies for MI treatment are still desirable. Previously studies reported the capacity of degradative fragment of h-HA (high molecular weight hyaluronic acid), hyaluronan oligosaccharides (<10 disaccharides units, o-HA), for wound healing by influence on angiogenesis, inspiring us to study its potential for myocardial functional recovery against MI. However, there are few reports about o-HA in MI therapy.

Methods: In our study, we synthesized o-HA with 6~10 disaccharides (4-5 kDa) by enzymatic degradation and investigated its therapeutic effects on MI.

Results: We found that o-HA could reduce infarct size and apoptosis in MI region, also promote myocardial angiogenesis and myocardial function reconstruction in MI mouse model. Furthermore, our results also indicated that o-HA in cardiac improved polarization of M2 type macrophage, removed the inflammatory response caused by neutrophil for accelerating myocardial function reconstruction in vivo. The transcriptomic analyses revealed that o-HA could activate expression of chemokines Ccl2 and Cxcl5 for promoting macrophage polarization and stimulate MAPK and JAK/STAT signaling pathway for compensatory response of myocardial function.

Conclusion: Collectively, our results suggested o-HA with 6~10 disaccharides might be a potential agent for reconstruction of cardiac function against MI.

Keywords: hyaluronic acid oligosaccharides, myocardial infarction, M2 macrophage, neutrophil, LV remodeling, angiogenesis