Proangiogenic potency of MUC18 in arteriosclerotic disease.
OBJECTIVE
Stenotic peripheral and dilatative arteriosclerotic diseases have different pathomechanism although associations between both diseases are well known. The adhesion molecule MUC18 is a cell membrane glycoprotein also known as the melanoma cell adhesion molecule. As MUC18 has proangiogenic potency in melanoma and prostate cancer this study investigated the role of MUC18 in patients with stenotic or dilatative arteriosclerotic disease as a putative biochemical marker.


METHODS
Using qRT-PCR, Western Blot and immunohistochemistry techniques, the expression of MUC18 in arteriosclerotic arteries from major lower limb amputates (AP, N.=15) as well as specimen from femoral endarterectomies (TEA, N.=20) and in dilatative aortic diseases using abdominal aortic aneurysms (AAA, N.=13) was evaluated. Human visceral arteries without macroscopic arteriosclerosis from liver transplants served as controls (AN, N.=19).


RESULTS
MUC18 mRNA and protein expression could be found in AN, AP, TEA and AAA tissues. Immunohistochemical analysis showed that a complete and intact intima was the predominant location of MUC18 expression. Although in stenotic arteriosclerotic disease (AP and TEA) the intima was widely calcified, qRT-PCR analysis showed overexpression compared to normal tissue. Interestingly, MUC18 expression was significantly down-regulated in dilatative compared to stenotic arteriosclerotic disease and normal arteries.


CONCLUSIONS
In peripheral stenotic arteriosclerotic disease the proangiogenic potency of MUC18 may play a role in angiogenesis of collaterals, whereas in dilatative aortic diseases the induction of collaterals is typically not evident. The results support the hypothesis of a role in angiogenesis of MUC18 in stenotic arteriosclerotic disease.
Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany - anne.kauffels@uks.eu.
R
R
Shayesteh-Kheslat
A
A
Kauffels
C
C
Rubie
V O
VO
Frick
M
M
Wagner
O
O
Kollmar
M K
MK
Schilling
D000368:Aged; D001012:Aorta, Abdominal / Q000737:chemistry* / Q000503:physiopathology / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D015153:Blotting, Western; D051929:CD146 Antigen / Q000032:analysis / Q000235:genetics; D016022:Case-Control Studies; D003097:Collateral Circulation; D003251:Constriction, Pathologic; D005260:Female; D005263:Femoral Artery / Q000737:chemistry* / Q000503:physiopathology / Q000601:surgery; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D018919:Neovascularization, Physiologic; D058729:Peripheral Arterial Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D051929:CD146 Antigen; D005819:Genetic Markers; C497902:MCAM protein, human; D012333:RNA, Messenger