Angiogenesis

, Volume 15, Issue 3, pp 377–389

Niacin improves ischemia-induced neovascularization in diabetic mice by enhancement of endothelial progenitor cell functions independent of changes in plasma lipids

  • Po-Hsun Huang
  • Chih-Pei Lin
  • Chao-Hung Wang
  • Chia-Hung Chiang
  • Hsiao-Ya Tsai
  • Jia-Shiong Chen
  • Feng-Yen Lin
  • Hsin-Bang Leu
  • Tao-Cheng Wu
  • Jaw-Wen Chen
  • Shing-Jong Lin
Original Paper

DOI: 10.1007/s10456-012-9267-z

Cite this article as:
Huang, P., Lin, C., Wang, C. et al. Angiogenesis (2012) 15: 377. doi:10.1007/s10456-012-9267-z

Abstract

Niacin was shown to inhibit acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids. Here, we investigated whether niacin can increase blood flow recovery after tissue ischemia by enhancing endothelial progenitor cell (EPC) functions in diabetic mice. Starting at 4 weeks after the onset of diabetes, vehicle or niacin (40 mg/kg/day) was administered daily by gavage to streptozotocin (STZ)-induced diabetic mice and diabetic endothelial nitric oxide synthase (eNOS)-deficient mice. Unilateral hindlimb ischemia surgery was conducted after 2 weeks of vehicle or niacin treatment. Compared to the control group, the niacin group had significantly increased ischemic/non-ischemic limb blood perfusion ratio and higher capillary density. These effects were markedly reduced in STZ-induced diabetic eNOS-deficient mice. Flow cytometry analysis showed impaired EPC-like cell (Sca-1+/Flk-1+) mobilization after ischemia surgery in diabetic mice but augmented mobilization in the mice treated with niacin. Diabetes was induced by administering STZ to FVB mice that received eGFP mouse bone marrow cells to evaluate effects of niacin on bone marrow-derived EPC homing and differentiation to endothelial cells. Differentiation of bone marrow-derived EPCs to endothelial cells in the ischemic tissue around vessels in diabetic mice that received niacin treatment, was significantly increased than that in control group. By in vitro studies, incubation with niacin in high-glucose medium reduced H2O2 production, cell apoptosis, and improved high glucose-suppressed EPC functions by nitric oxide-related mechanisms. Our findings demonstrate that niacin increases blood flow recovery after tissue ischemia in diabetic mice through enhancing EPC mobilization and functions via nitric oxide-related pathways.

Keywords

NiacinDiabetesIschemiaEndothelial progenitor cellsNitric oxide

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Po-Hsun Huang
    • 1
    • 5
    • 6
    • 7
  • Chih-Pei Lin
    • 3
    • 8
  • Chao-Hung Wang
    • 6
    • 7
    • 10
  • Chia-Hung Chiang
    • 1
    • 7
  • Hsiao-Ya Tsai
    • 6
  • Jia-Shiong Chen
    • 9
  • Feng-Yen Lin
    • 11
    • 12
  • Hsin-Bang Leu
    • 1
    • 4
    • 6
    • 7
  • Tao-Cheng Wu
    • 1
    • 7
  • Jaw-Wen Chen
    • 1
    • 2
    • 7
    • 9
  • Shing-Jong Lin
    • 1
    • 2
    • 6
    • 7
  1. 1.Division of Cardiology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Department of Medical Research and EducationTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Department of Pathology and Laboratory MedicineTaipei Veterans General HospitalTaipeiTaiwan
  4. 4.Healthcare and Management CenterTaipei Veterans General HospitalTaipeiTaiwan
  5. 5.Department of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  6. 6.Institute of Clinical MedicineNational Yang-Ming UniversityTaipeiTaiwan
  7. 7.Cardiovascular Research CenterNational Yang-Ming UniversityTaipeiTaiwan
  8. 8.Department of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in MedicineNational Yang-Ming UniversityTaipeiTaiwan
  9. 9.Institute and Department of PharmacologyNational Yang-Ming UniversityTaipeiTaiwan
  10. 10.Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial HospitalKeelung, and Chang Gung University College of MedicineTaoyuanTaiwan
  11. 11.Department of Internal Medicine, School of MedicineTaipei Medical UniversityTaipeiTaiwan
  12. 12.Division of CardiologyTaipei Medical University HospitalTaipeiTaiwan