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Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Proangiogenic potency of MUC18 in arteriosclerotic disease
R Shayesteh-Kheslat1, A Kauffels, C Rubie
1Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany - anne.kauffels@uks.eu.
Aim:
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.
Conclusion:
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.
Insights
Muc18, an adhesion molecule, is overexpressed in stenotic arteriosclerotic disease, suggesting a role in collateral angiogenesis. Its expression is down-regulated in dilatative aortic diseases, indicating distinct roles in different arteriosclerotic conditions.
Area of Science:
- Vascular Biology
- Biochemistry
- Oncology
Background:
- Arteriosclerotic diseases encompass both stenotic and dilatative conditions with distinct pathomechanisms.
- The adhesion molecule MUC18 (melanoma cell adhesion molecule) exhibits proangiogenic properties in cancer.
- Understanding MUC18's role in arteriosclerosis may reveal novel biochemical markers.
Purpose of the Study:
- To investigate the expression and role of MUC18 in stenotic and dilatative arteriosclerotic diseases.
- To evaluate MUC18 as a potential biochemical marker for different arteriosclerotic conditions.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for mRNA expression.
- Western Blot and immunohistochemistry for protein expression analysis.
- Analysis of MUC18 expression in human artery tissues from lower limb amputates, femoral endarterectomies, abdominal aortic aneurysms, and healthy controls.
Main Results:
- MUC18 mRNA and protein were detected in all evaluated arterial tissues.
- Overexpression of MUC18 was observed in stenotic arteriosclerotic disease (lower limb amputates and femoral endarterectomies) compared to controls.
- MUC18 expression was significantly downregulated in dilatative aortic diseases (abdominal aortic aneurysms) compared to stenotic disease and normal arteries.
Conclusions:
- MUC18's proangiogenic potential may contribute to collateral angiogenesis in peripheral stenotic arteriosclerotic disease.
- The reduced expression of MUC18 in dilatative aortic diseases suggests a different role, potentially not involving significant collateral induction.
- MUC18 is a promising marker for understanding angiogenesis in stenotic arteriosclerotic conditions.

