Dysfunctional vasa vasorum in diabetic peripheral artery obstructive disease with critical lower limb ischaemia.
OBJECTIVE
To establish whether in diabetic patients with peripheral artery obstructive disease (PAOD) vasa vasorum (vv) neoangiogenesis is altered with increased arterial damage.


METHODS
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.
Orrico
C
C
Department of Specialistic Surgical and Anaestesiological Sciences, S. Orsola-Malpighi Hospital - University of Bologna, Via Massarenti, 9 Bld 5, 40126 Bologna, Italy. catia.orrico2@unibo.it
Pasquinelli
G
G
Foroni
L
L
Muscarà
D
D
Tazzari
P L
PL
Ricci
F
F
Buzzi
M
M
Baldi
E
E
Muccini
N
N
Gargiulo
M
M
Stella
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D001157:Arterial Occlusive Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D016638:Critical Illness; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007558:Italy; D035002:Lower Extremity / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014651:Vasa Vasorum / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D014841:von Willebrand Factor / Q000032:analysis
D018952:Antigens, CD34; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor