Identification of endothelial-derived proteins in plasma associated with cardiovascular risk factors

Abstract

Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease (CVD) risk factors, such as smoking and obesity. Risk factor exposure can modify EC signalling and behaviour, leading to arterial and venous disease development. Biomarker panels to assess EC dysfunction are lacking, but could be useful for risk stratification and to monitor treatment response. Here, we used affinity proteomics to identify EC-derived proteins circulating in plasma that were associated with CVD risk factor exposure. 216 proteins, known to be expressed in ECs across vascular beds, were measured in plasma samples (n=1005) from the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot. We identified 38 EC-derived proteins that were associated with body mass index, total cholesterol, low density lipoprotein, smoking, hypertension or diabetes. Sex-specific analysis revealed female- and male-only associations were most frequently observed with BMI, or total cholesterol, respectively. We showed a relationship between individual CVD risk, calculated with the Framingham risk score, and the corresponding biomarker profiles; presenting the concept of measuring EC-derived proteins in plasma to infer vascular status.

An Update on Safe Anticoagulation

“…34 However, in contrast to FXII deficiency, low FXI activity is associated with bleeding termed “hemophilia C.” Bleeding in FXI deficiency is mild; however, it is rather unpredictable, as it is not linked to circulating FXI antigen levels and biomarkers to assess vascular disease and bleeding risk in these patients are currently lacking. 35 Despite the striking phenotype in FXI-deficient (F11 −/− ) mice, the discovery of impaired thrombus formation in these animals did not raise much attention most probably because the underlying mechanism was misinterpreted. Originally it was believed that impaired thrombosis in F11 −/− mice resulted from defective FXI activation by thrombin that in turn was produced by tissue factor (“feedback activation loop”).…”

The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease

“…4 21 22 Potential prognostic biomarker in cardiovascular disease (CVD). 11 23 24 Released from Weibel-Palade bodies of endothelial cells (ECs). 21 Upregulated by inflammatory stimuli, counteracting the vascular protective effects of angiopoietin-1 (ANGPT1) 11 21 22…”