Two C‐C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm

Abstract

BackgroundInflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (AAA). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA.Methods and ResultsTissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T‐cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP‐1b), had increased expression in AAA, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA‐free controls (n=970) suggested a (risk factor adjusted) AAA‐association with eotaxin, RANTES, and high sensitivity C‐reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI, 3.5–6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking.ConclusionsContrary to reports suggesting a distinct T helper 2–associated inflammatory profile in AAA, this current study suggests a more‐generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as AAA biomarkers.

T Cells Are Dominant Population in Human Abdominal Aortic Aneurysms and Their Infiltration in the Perivascular Tissue Correlates With Disease Severity

“…Elevated expression of CCR5 in PVT containing CD4 + and CD8 + cells as well as a differential expression of these cells between AAA wall and PVT (seen for CD4 + T cells) provides a hint for the role of RANTES chemokine in T cell recruitment to PVT and AAA wall. This data, coupled with the fact that RANTES is upregulated within the adventitia of human AAA (8) may suggest a role for this chemokine in the regulation of T cell trafficking in AAA, which has been demonstrated in relation to many other risk factors of AAA such as hypertension (50). Furthermore, angiotensin II induced expression of RANTES within the vasculature and CCR5 on T cells is thought to mediate T cell accumulation within the PVAT and adventitia in a mouse model of hypertension (47) indicating the importance of this chemotactic axis in both mice and humans.…”

“…The mechanisms of AAA, defined primarily in animal model studies, are complex, involving smooth muscle cell apoptosis, oxidative stress (4), and inflammation (5). Clinically, patients with AAA have elevated circulating pro-inflammatory cytokines (6–8) and immunohistochemical studies of AAA reveal the presence of inflammatory cells such as macrophages, T cells, B cells, dendritic cells, natural killer cells, neutrophils, and mast cells (9–14).…”

Heme oxygenase-1 deficiency exacerbates angiotensin II-induced aortic aneurysm in mice

“…A recent study suggested eotaxin to be an independent plasma biomarker for AAA [24]. Moreover, eotaxin has been reported to induce pro-MMP2 expressions in VSMCs [25].…”

Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure)

“…Eosinophil chemoattractant Plays a role in the pathogenesis of several allergic conditions (e.g. asthma) (Williams, 2015) Increased in eosinophilic myocarditis (Diny et al, 2016), abdominal aortic aneurysms (Jones, Phillips, Williams, van Rij, & Kabir, 2016) and CAD (Economou et al, 2001).…”