Expression of a Disintegrin and Metalloprotease in Human Abdominal Aortic Aneurysms

Abstract

Objectives: The a disintegrin and metalloprotease (ADAM) family of metalloproteases possesses a proteolytic function and activates various inflammatory factors. Their expression pattern in an abdominal aortic aneurysm (AAA) is as yet unknown. The aim of this study was to make a detailed analysis of the expression of ADAMs 8, 9, 10, 12, 15 and 17, and their tissue inhibitors of metalloprotease (TIMP)-1 and TIMP-3 in patients with AAA. Design: The aortic vessel walls of AAA patients (n = 20) and non-aneurysmal aortic specimens (n = 10) were obtained by conventional surgical repair and autopsy. SYBR green-based real-time PCR, histology and immunohistochemistry were performed on all samples. Main Outcome Measures: Quantitative expression analysis and the localisation of various ADAMs in AAA. Results: ADAMs tested in our study were expressed in both AAA and control aorta without any significant differences between the groups. In contrast, expression of TIMP-1 was significantly reduced in AAA compared to control vessels. Smooth muscle cells (SMCs), neovessels and macrophages were positive for all ADAMs and TIMPs tested. Infiltrates were negative for TIMP-3, and luminal endothelial cells were positive for ADAMs 15 and 17. A significant positive correlation was observed between ADAMs 10, 12, 15, 17, TIMP-3 and SMCs. Conclusion: ADAMs are constitutively expressed in normal aortic vessel walls and AAA, particularly in SMCs.

ADAMTS-1 in abdominal aortic aneurysm

“…The most studied family of matrix-degrading enzymes, which we also contributed to, is probably the matrix metalloproteinases (MMPs) since these proteases are capable to degrade plenty of macromolecules present in the connective tissue matrix [1–3]. The extensive family of matrix metalloproteases beside MMPs includes a disintegrin and metalloproteinase (ADAMs) of which several members have been found in tissue from abdominal aortic aneurysms (AAA) [4, 5]. …”

Analysis of <b><i>ADAM17</i></b> Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm

“…ADAMs 8, 9, 10, 12, 15 and 17 were found to be expressed in both AAA and control aorta [19], and ADAM17 (TACE) was upregulated in human AAA aortic specimens and was associated with chronic inflammation, increased neoangiogenesis and ECM disruption [9]. The role that ADAM17 plays in the inflammation and proteolytic degradation of ECM in the vessel wall markedly contributes to the formation and rupture of an AAA [5,6].…”

Expression of matrix metalloproteinases and their inhibitors in the internal carotid artery wall in pathological tortuosity

“…Так, в формировании аневризмы аорты ведущую роль играет потеря эластина и коллагена, причиной чего служит повышение продукции различных типов протеаз, в том числе ММП-1, 2 и 9 [14,15]. При этом экспрессия тканевых ингибиторов матриксных металлопротеиназ (ТИМП-1 и ТИМП-2) понижена, что приводит к разрушению компонентов ВКМ стенки аневризмы [16,17]. Необходимым условием нормального протекания физиологических процессов является поддержание равновесия между активностью ММП и их ингибиторов.…”

“…Вместе с тем, как показали результаты работ W. Wilson, E. Schwalbe (2005), а также C. Lipp и соавт. (2012), уровень ингибиторов металлопротеиназ ТИМП-1 и ТИМП-2 снижен в аневризмах брюшного отдела аорты по сравнению с нормальной аортой, что приводит к деградации компонентов ВКМ [16,17].…”