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

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.