Inflammatory cell infiltrates, hypoxia, vascularization, pentraxin 3 and osteoprotegerin in abdominal aortic aneurysms – A quantitative histological study

Abstract

Information about the tissue characteristics of abdominal aortic aneurysms (AAAs), some of which may be reflected in the serum, can help to elucidate AAA pathogenesis and identify new AAA biomarkers. This information would be beneficial not only for diagnostics and follow-up but also for potential therapeutic intervention. Therefore, the aim of our study was to compare the expression of structural proteins, immune factors (T and B lymphocytes, macrophages, neutrophils and pentraxin 3 (PTX3)), osteoprotegerin (OPG), microvessels and hypoxic cells in AAA and nonaneurysmal aortic walls. We examined specimens collected during surgery for AAA repair (n = 39) and from the abdominal aortas of kidney donors without AAA (n = 8). Using histochemical and immunohistochemical methods, we quantified the areas positive for smooth muscle actin, desmin, elastin, collagen, OPG, CD3, CD20, MAC387, myeloperoxidase, PTX3, and hypoxia-inducible factor 1-alpha and the density of CD31-positive microvessels. AAA samples contained significantly less actin, desmin, elastin and OPG, more collagen, macrophages, neutrophils, T lymphocytes, B lymphocytes, hypoxic cells and PTX3, and a greater density of vasa vasorum (VV) than those in non-AAA samples. Hypoxia positively correlated with actin and negatively correlated with collagen. Microvascular density was related to inflammatory cell infiltrates, hypoxia, PTX3 expression and AAA diameter. The lower OPG expression in AAAs supports the notion of its protective role in AAA remodeling. AAA contained altered amounts of structural proteins, implying reduced vascular elasticity. PTX3 was upregulated in AAA and colocalized with inflammatory infiltrates. This evidence supports further evaluation of PTX3 as a candidate marker of AAA. The presence of aortic hypoxia, despite hypervascularization, suggests that hypoxia-induced neoangiogenesis may play a role in AAA pathogenesis. VV angiogenesis of the AAA wall increases its vulnerability.

Use of MALDI Mass Spectrometry Imaging to Identify Proteomic Signatures in Aortic Aneurysms after Endovascular Repair

“…Collagen, as the main structural protein in the aortic wall, mainly consists of fibrillar collagens type I and III, accounting for 80–90% of the total collagen. Both increased collagen I/III levels enhancing arterial stiffness and decreased collagen I/III levels weakening the aortic wall have been proven to favor aortic aneurysm and dissection [ 46 , 47 ]. Augmented expression of MMPs is well documented in human and mouse aortic aneurysm [ 48 ] leading to degradation of aortic ECM and collagen cleavage in particular.…”

“…Desmin, actin, and tubulin [ 52 ] can be used to define contractile phenotype in VSMC. In comparison to non-AAA samples, AAA samples contain significantly less actin and desmin, suggesting higher levels of synthetic VSMC in AAA patients [ 47 ].…”

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

“…A study has revealed the potential role of hypoxia-mediated new vessel formation in the pathogenic mechanism of AAAs [ 106 ]. Dang et al examined the expression patterns of circRNAs in hypoxia-stressed human umbilical vein endothelial cells (HUVECs) and detected the notable upregulation of hsa_circ_0010729.…”

Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm

“…In the adventitia, small blood vessels called the vasa vasorum (VV) oxygenate the aortic wall [ 4 ]. Abnormal diffusion of oxygen to the aortic wall causes local hypoxia, which is associated with vascular remodeling [ 5 , 6 ]. In a previous study, we reported that VV stenosis causes hypoperfusion of the human abdominal aortic wall [ 7 ].…”