Potential role for anti‐angiogenic therapy in abdominal aortic aneurysms

Abstract

Objective Abdominal aortic aneurysm (AAA) is a condition that mainly affects elderly men. At present, there is no effective medical therapy that can retard aneurysm growth or prevent aneurysm rupture. There is evidence that angiogenesis within the wall of an aortic aneurysm may play key roles in aneurysm progression as well as rupture. The use of anti-angiogenic therapy as potential medical therapy in AAA is a promising strategy but has never been studied in detail.Design This paper discusses the basic mechanisms of angiogenesis, the role played by angiogenesis in aortic aneurysms and the potential therapeutic role of anti-angiogenic drugs against aneurysm expansion or rupture.Results Angiogenesis is a multi-step process which is fundamental for growth and differentiation of various tissues within a multi-cellular organism. Hypoxia and inflammation are key stimuli for activation of neoangiogenesis. Investigations in both human tissues and animal models of AAA have shown that angiogenesis is a pathological hallmark of AAA and appears to play a role in the development and progression of the condition. Pre-clinical studies have shown that anti-angiogenic drugs can potentially be effective in reducing the intensity of aneurysm formation, suggesting that such drugs may potentially be useful as novel drug therapy for AAA in humans.Conclusion Current evidence suggests that angiogenesis contributes to the destructive processes within aneurysmal aortic wall. As novel drug therapy for aortic aneurysms (for use in humans) is still eluding researchers, anti-angiogenic pathway appears to be an attractive approach.

Lymphangiogenesis and Angiogenesis in Abdominal Aortic Aneurysm

“…Angiogenesis is thought to contribute to destructive processes within the AAA wall and plays a key role in aortic aneurysm development and rupture [7]. Therefore, various anti-angiogenic agents have been studied in animal models for potential treatment of AAA [30], [49], [50]. Maruyama et al reported that down-regulation of VEGFR-3 and subsequent inhibition of lymphangiogenesis delayed diabetic wound healing in a mouse model [51].…”

PET Imaging of Abdominal Aortic Aneurysm with 64Cu-Labeled Anti-CD105 Antibody Fab Fragment

“…Angiogenesis has been proven to be a pathological hallmark of AAA in both human and animal models, and it plays an important role in the development and progression of AAA (12–15). Higher levels of neovascularization are detected at the rupture edge in aortic aneurysm, suggesting that imaging of molecules and processes involved in angiogenesis can potentially depict high-risk aneurysms (16).…”

Extra- and Intraluminal Elastase Induce Morphologically Distinct Abdominal Aortic Aneurysms in Mice and Thus Represent Specific Subtypes of Human Disease

“…Angiogenesis in the adventitia and media, along with CD34+ cell infiltration, is a general observation in human AAA, depending on intima/media thickness and the grade of inflammation. This is currently under investigation with the treatment of angiogenesis inhibitors [28]. …”