Endothelial dysfunction in patients with eosinophilic granulomatosis with polyangiitis

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p < 0.001) and 41.9% of thrombomodulin (p < 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (p < 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (β = - 0.3 [95% confidence interval (CI) - 0.5 to - 0.1]), serum level of IL-6 (β = - 0.36 [95% CI - 0.62 to - 0.1]), and thrombomodulin (β = - 0.34 [95% CI - 0.6 to - 0.08]). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.

Impact of Cardiovascular Risk Factors on the Occurrence of Cardiovascular Events in Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitides

“…For example, ANCAs may trigger the release of bioactive molecules that have a role in thrombosis, inflammation, and endothelial activation [ 19 ]. This endothelial dysfunction is more prevalent in AAV patients as compared to the general population [ 20 , 21 , 22 ], is associated with the presence of inflammation proteins, particularly during vasculitis flares [ 21 , 22 ], and contributes to fibrosis, thrombosis, and atherosclerosis, beginning with preclinical target organ damage followed by overt CVD [ 23 , 24 ]. In EGPA patients, eosinophils could also have a direct role in endothelial cell injury [ 22 ].…”

Tofacitinib suppressed remodeling of pulmonary eosinophilic vasculitis in a murine model

“…Several inflammatory diseases-including rheumatoid arthritis, inflammatory bowel disease, vasculitis, and several types of cancer-have been associated with IL-6 [26]. Furthermore, a recent study has shown that an increased serum IL-6 level occurred parallel to endothelial dysfunction in EGPA [27], suggesting it may play an important role in this disease. A previous study demonstrated that blocking the IL-6R with an antibody led to reduced Th2 cytokines and eosinophils in the lungs of OVA-sensitized mice [28].…”

Endothelial dysfunction in patients with systemic sclerosis

“…Celemayer’s method was used to measure FMD of the brachial artery [ 22 ]. We used the technique described in detail in our previous papers [ 23 , 24 ]. The baseline sagittal diameter (D1) of a distal part of the brachial artery was measured in the M-presentation with a 10 MHz linear array ultrasonic transducer placed 2–3 cm proximal to the arterial bifurcation.…”

“…As previously described by us, the IMT of the carotid artery was measured by ultrasound with a 10 MHz linear transducer. The thickness of the anterior and posterior walls of the common carotid arteries was measured in the longitudinal projection immediately proximal to their bifurcation [ 23 , 24 ]. We recorded the mean value of the IMT on the right and left side for analysis.…”