Abstract
Abdominal aortic aneurysms (AAA) are a significant cause of premature deaths worldwide. Since there is no specific treatment for reducing AAA progression, it is crucial to understand the pathogenesis leading to aneurysm wall weakening/remodeling and identify new proteins involved in this process which could subsequently serve as novel therapeutic targets. In this study, we analyzed the presence of the hypoxia-related proteins carbonic anhydrase IX (CA IX), hypoxia-inducible factor 1α (HIF-1α), and AKT as the key molecule in the phosphoinositide-3-kinase pathway in the AAA wall. Additionally, we used a blood-based assay to examine soluble CA IX (s-CA IX) levels in the plasma of AAA patients. Using western blotting, we detected CA IX protein in 12 out of 15 AAA tissue samples. Immunohistochemistry staining proved CA IX expression in the media of the aneurysmal wall. Evaluation of phosphorylated (p-AKT) and total AKT showed elevated levels of both forms in AAA compared to normal aorta. Using ELISA, we determined the concentration of s-CA IX >20 pg/mL in 13 out of 15 AAA patients. Results obtained from in silico analysis of CA9 and aneurysm-associated genes suggest a role for CA IX in aneurysmal wall remodeling. Our results prove the presence of hypoxia-related CA IX in AAA tissues and indicate a possible role of CA IX in hypoxia-associated cardiovascular diseases.
Highlights
Abdominal aortic aneurysm is defined as an enlargement of the infrarenal or suprarenal aorta to a diameter of at least 3 cm
By determination of plasma carbonic anhydrase IX (CA IX) values using an enzyme-linked immunosorbent assay (ELISA) we evaluated the concentration of soluble CA IX (s-CA IX) in plasma samples from Abdominal aortic aneurysms (AAA) patients suggesting the presence of s-CA IX in hypoxia-related cardiovascular diseases
Since CA IX expression is triggered in hypoxic conditions via hypoxia-inducible factors (HIFs)-1-mediated transcriptional activation [16], we examined the expression of the oxygen-regulated α subunit of hypoxia-inducible factor 1 (HIF-1) transcription factor in AAA tissues
Summary
Abdominal aortic aneurysm is defined as an enlargement of the infrarenal or suprarenal aorta to a diameter of at least 3 cm. Many of the processes leading to AAA development still remain unclear, recent studies have shown that key pathophysiological features of AAA include chronic inflammation [2], extracellular matrix degradation [3], vascular smooth muscle cell (VSMCs) phenotype modulation, VSMCs apoptosis [4], and hypoxia [5]. In the wall of large arteries, luminal blood diffusion is the main source of nutrients and oxygen for the cells located on the luminal side, while perfusion via vasa vasorum provides nourishment to the cells located on the abluminal side. Any alteration in these processes, or a change in oxygen consumption by cells, creates a hypoxic microenvironment [6]. The adaptation of cells to hypoxic stress is regulated by hypoxia-inducible factors (HIFs), which mediate the expression of over 100 genes involved in important signaling pathways [7]
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