, Volume 22, Issue 1, pp 53–65 | Cite as

Inhibition of macrophage inflammatory protein-1β improves endothelial progenitor cell function and ischemia-induced angiogenesis in diabetes

  • Ting-Ting Chang
  • Liang-Yu Lin
  • Jaw-Wen ChenEmail author
Original Paper


Systemic inflammation might contribute to the impairment of neovasculogenesis and endothelial progenitor cell (EPC) function in clinical diabetes mellitus (DM). Macrophage inflammatory protein-1β (MIP-1β) is an inflammatory chemokine that may be up-regulated in clinical DM. Its role in diabetic vasculopathy was not clarified. This study aimed to investigate the role of MIP-1β in human EPCs and in neovasculogenesis in different diabetic animal models with hindlimb ischemia. EPCs chamber assay and in vitro tube formation assay were used to estimate the degree of EPC migration and tube formation abilities. Leprdb/JNarl mice, C57BL/6 mice fed a high-fat diet, and streptozotocin-induced diabetic mice were used as different diabetic animal models. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neovasculogenesis and the circulating levels of EPCs, respectively. MIP-1β impaired human EPC function for angiogenesis in vitro. Plasma MIP-1β levels were up-regulated in type 2 DM patients. MIP-1β inhibition enhanced the function and the C-X-C chemokine receptor type 4 expression of EPCs from type 2 diabetic patients, and improved EPC homing for ischemia-induced neovasculogenesis in different types of diabetic animals. MIP-1β directly impaired human EPC function. Inhibition of MIP-1β improved in vitro EPC function, and enhanced in vivo EPC homing and ischemia-induced neovasculogenesis, suggesting the critical role of MIP-1β for vasculopathy in the presence of DM.


Angiogenesis Diabetes mellitus Endothelial progenitor cell Inflammation Ischemia Macrophage inflammatory protein-1β 



This study was partially supported by research grants V105E18-004-MY3, V105C-117, and V104C-101 from the Taipei Veterans General Hospital, Taipei, Taiwan.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Institute of PharmacologyNational Yang-Ming UniversityTaipeiTaiwan, ROC
  2. 2.Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan, ROC
  3. 3.Division of Clinical Research, Department of Medical ResearchTaipei Veterans General HospitalTaipeiTaiwan, ROC
  4. 4.Cardiovascular Research CenterNational Yang-Ming UniversityTaipeiTaiwan, ROC

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