A Pilot Study of Protein Microarray for Simultaneous Analysis of 274 Cytokines Between Abdominal Aortic Aneurysm and Normal Aorta

Abstract

Cytokines play an important role in the pathogenesis of abdominal aortic aneurysm (AAA). We evaluated the cytokine expression profile of large AAA walls using a 274-cytokine protein array. We hypothesized that AAAs are characterized by an inflammatory, chemotactic cytokine profile. We investigated the cytokine expression profile of 12 patients with AAA and 6 nonaneurysmal controls using an antibody-based protein array. The array generated antibodies against homogenized human aortic tissues to validate the cytokines differentially expressed in AAAs and normal aortas. Data were quantified using fluorescent signal intensities and statistically analyzed by the t test. Fifty-nine cytokines were differentially expressed between the AAA and control samples. Of the 35 selected cytokines that had relative expression >1000, 29 were significantly higher and 6 were lower in AAA samples than in controls. They respectively belonged to CC chemokines, CXC chemokines, pro-inflammatory cytokines, growth factors, proteolytic proteins and inhibitors, and cell adhesion cytokines. Our results show that distinct cytokines are involved in AAAs and suggest that the pathways involving these cytokines may be associated with the pathogenesis and development of AAAs. These findings, if confirmed by larger studies, may suggest treatment targets.

Dysregulations of Key Regulators of Angiogenesis and Inflammation in Abdominal Aortic Aneurysm

“…This result suggests that enhanced angiogenesis is involved in the AAA pathogenesis, as PDGFA is a strong stimulator of this process [38,39]. A similar result for PDGFA was obtained in previous studies using a membrane-based complementary DNA expression array and immunohistochemical staining of tissues, in which PDGFA was significantly upregulated in AAA compared to the control samples [40,41]; however, the other study showed lower expression of PDGFA in aneurysm vs. normal aorta [42]. This discrepancy could result from a type of aneurysm and the site where tissue sample was collected, since, previously, a higher expression of PDGFA, together with PDGFB, was detected in small vessels of the aneurysmal walls of atherosclerotic AAA, but in inflammatory AAA this expression was significantly lower [43].…”

Expression of MMP-2, MMP-9, and NGAL in Tissue and Serum of Patients with Vascular Aneurysms and Their Modulation by Statin Treatment: A Pilot Study

“…In this view, recently, we documented that vascular damage induces an inflammatory response that can evoke a local reaction with the activation and recall of cytokines and inflammatory mediators [33] involved in aneurysmal diseases [32,34]. In an interesting pilot study, Yuwen et al [35], investigating the expression of a plethora of cytokines in patients with aortic aneurysmal disease compared to healthy patients, described the role of several cytokines (i.e., CC chemokines, CXC chemokines, proinflammatory cytokines, growth factors, proteolytic proteins, and cell adhesion cytokines) in the pathogenesis of the aneurysms. In this study, several cytokines (e.g., IL-1α, IL-1β, IL-2, and IL-17) and growth factors (e.g., insulin-like growth factor-1, transforming growth factor-α, and tumor necrosis factor-α) were reported to activate NGAL, a marker of neutrophil activation [36] that is involved in tissue injury [37,38].…”

Identification of key genes and pathways in abdominal aortic aneurysm by integrated bioinformatics analysis

“…In accordance with previous reports, some proinflammatory cytokines, chemokines, proteolytic proteins, and aneurysmrelated GO entries were identified in the pathogenesis and development of AAA. 27,28 By using the emerging singlecell sequencing technique, we further explored the cell-specific expression of these hub genes. The PPI and single-cell sequencing analysis identified four hub genes involved in the progression of AAA.…”