Dysfunctional vasa vasorum in diabetic peripheral artery obstructive disease with critical lower limb ischaemia

Eur J Vasc Endovasc Surg. 2010 Sep;40(3):365-74. doi: 10.1016/j.ejvs.2010.04.011. Epub 2010 Jun 1.

Abstract

Objectives and design: To establish whether in diabetic patients with peripheral artery obstructive disease (PAOD) vasa vasorum (vv) neoangiogenesis is altered with increased arterial damage.

Materials: Thirty-three patients with PAOD and critical lower limb ischaemia, 22 with type II diabetes.

Methods: Immunohistochemistry for endothelial cell markers (CD34 and von Willebrand Factor); real-time reverse transcription polymerase chain reaction (RT-PCR) to quantify arterial wall expression of vascular endothelial growth factor (VEGF); enzyme-linked immunosorbent assay (ELISA) to assess blood VEGF; flow cytometry to detect circulating endothelial cells (CECs).

Results: Patients with PAOD and diabetes have a higher frequency (60% vs. 45%) of advanced atherosclerotic lesions and a significant reduction (p = 0.0003) in CD34(+) capillaries in the arterial media. Adventitial neoangiogenesis was increased equally (CD34(+) and vWF(+)) in all patients. Likewise, all patients have increased CEC and VEGF concentration in the blood as well as in-situ VEGF transcript expression.

Conclusions: Patients with PAOD have remarkable arterial damage despite increased in-situ and circulating expression of the pro-angiogenic VEGF; a dysfunctional vv angiogenesis was seen in diabetics which also showed a higher frequency of parietal damage; it is suggested that in diabetic arterial wall, injury is worsened by vv inability to finalise an effective VEGF-driven arterial wall neoangiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / analysis
  • Arterial Occlusive Diseases / metabolism
  • Arterial Occlusive Diseases / pathology
  • Arterial Occlusive Diseases / physiopathology*
  • Case-Control Studies
  • Critical Illness
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / metabolism
  • Diabetic Angiopathies / pathology
  • Diabetic Angiopathies / physiopathology*
  • Endothelial Cells / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / physiopathology*
  • Italy
  • Lower Extremity / blood supply*
  • Lower Extremity / physiopathology*
  • Male
  • Middle Aged
  • Neovascularization, Physiologic*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vasa Vasorum / chemistry
  • Vasa Vasorum / pathology
  • Vasa Vasorum / physiopathology*
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / genetics
  • von Willebrand Factor / analysis

Substances

  • Antigens, CD34
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor