P-Hydroxybenzyl alcohol-containing biodegradable nanoparticle improves functional blood flow through angiogenesis in a mouse model of hindlimb ischemia

Byung Ryul Cho, Dong Ryeol Ryu, Kwang Soon Lee, Dong Keon Lee, Soochan Bae, Dong Goo Kang, Qingen Ke, Sylvia S. Singh, Kwon Soo Ha, Young Guen Kwon, Dongwon Lee, Peter M. Kang, Young Myeong Kim

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Therapeutic angiogenesis has achieved promising results for ischemic diseases or peripheral artery disease in preclinical and early-phase clinical studies. We examined the therapeutic angiogenic effects of HPOX, which is biodegradable polymer composing the antioxidant p-hydroxybenzyl alcohol (HBA), in a mouse model of hindlimb ischemia. HPOX effectively stimulated blood flow recovery, compared with its degraded compounds HBA and 1,4-cyclohexendimethanol, via promotion of capillary vessel density in the ischemic hindlimb. These effects were highly correlated with levels of angiogenic inducers, vascular endothelial cell growth factor (VEGF), heme oxygenase-1 (HO-1), and Akt/AMPK/endothelial nitric oxide synthase (eNOS) in ischemic mouse hindlimb muscle. Blood perfusion and neovascularization induced by HPOX were reduced in eNOS-/- and HO-1+/- mice. HPOX also elevated the endothelial cell markers VEGF receptor-2, CD31, and eNOS mRNAs in the ischemic hindlimb, indicating that HPOX increases endothelial cell population and angiogenesis in the ischemic muscle. However, this nanoparticle suppressed expression levels of several inflammatory genes in ischemic tissues. These results suggest that HPOX significantly promotes angiogenesis and blood flow perfusion in the ischemic mouse hindlimb via increased angiogenic inducers, along with suppression of inflammatory gene expression. Thus, HPOX can be used potentially as a noninvasive drug intervention to facilitate therapeutic angiogenesis.

Original languageEnglish
Pages (from-to)679-687
Number of pages9
JournalBiomaterials
Volume53
DOIs
Publication statusPublished - 2015 Jun 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MEST) ( NRF-2011-0028790 and NRF-2013M3A9B6046563 ), Korea Health Technology R&D Project ( HI13C13700000 ) funded by the Korea Ministry of Health & Welfare , and the Research Grant of Daiichi-Sankyo Korea Co., LTD. We thank Dr. Elaine Por for helpful comments and critical reading of this manuscript.

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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