Overexpression of αVβ3 Integrin in an Aortic Aneurysm Murine Model: Confirmation in Ex Vivo Human Abdominal Aortic Aneurysm Tissue and Its Potential Application for Molecular Imaging Characterisation
Javier E. Anaya-Ayala , Brenda J. Galicia-Vega , Jacqueline Mejía-Cervantes , Ezequiel Solano-Mendivil , Ingrid A. Landero-Aguilar , Brenda Marquina-Castillo , Carlos Bravo-Reyna , Carlos Serrano-Gavuzzo , Luis A. Medina-Velázquez , Carlos A. Hinojosa
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Abstract
Background
The pathophysiological mechanisms that occur in the wall of aortic aneurysms are not fully understood. Angiogenesis is a characteristic change in aneurysmal disease; αVβ3 integrin is a glycoprotein overexpressed in this biological process. This study aimed to evaluate angiogenic activity in a murine model of thoracic aortic aneurysm (TAA) using molecular imaging and immunofluorescence, and to assess differences in αVβ3 integrin expression in ex vivo human aneurysmal and non-diseased aortic tissues.
Methods
Eight Wistar rats underwent experimental induction of TAA with peri-adventitial calcium chloride (CaCl2) and were evaluated with micropositron emission tomography (MicroPET) using arginine-glycine-aspartate with gallium 68 (68Ga-RGD) as a radiotracer. The Wilcoxon test was used to compare the chemically induced site (aneurysm) and intact aortic tissue (control). Six months later, the specimens were euthanised and tissues were evaluated with immunofluorescence. For human aorta analysis, diseased and non-diseased arterial portions were obtained from 13 patients (mean age 67 years, 85% males) who underwent open abdominal aortic aneurysm repair and were evaluated with the same protocol as the experimental specimens.
Results
An overall MicroPET uptake was obtained in the murine models; the median standard uptake value of 68Ga-RGD in the aneurysm was 0.0125, while the uptake in controls was 0.0003 (p = 0.011). Immunofluorescence confirmed overexpression of integrin αVβ3 in the aneurysm wall in comparison with the control tissue (p < 001). Human aneurysmal samples also had a statistically significant overexpression of αVβ3 (p = 0.031).
Conclusions
Significant differences in the angiogenic process were demonstrated with molecular imaging and immunofluorescence in the murine TAA model. Differences in αVβ3 integrin expression were confirmed when comparing diseased and non-diseased aortas in humans.
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