Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis

To date, no plaque-derived blood biomarker is available to allow diagnosis, prognosis or monitoring of atherosclerotic vascular diseases. In this study, specimens of thrombendarterectomy material from carotid and iliac arteries were incubated in protein-free medium to obtain plaque and control secretomes for subsequent subtractive phage display. The selection of nine plaque secretome-specific antibodies and the analysis of their immunopurified antigens by mass spectrometry led to the identification of 22 proteins. One of them, junction plakoglobin (JUP-81) and its smaller isoforms (referred to as JUP-63, JUP-55 and JUP-30 by molecular weight) were confirmed by immunohistochemistry and immunoblotting with independent antibodies to be present in atherosclerotic plaques and their secretomes, coronary thrombi of patients with acute coronary syndrome (ACS) and macrophages differentiated from peripheral blood monocytes as well as macrophage-like cells differentiated from THP1 cells. Plasma of patients with stable coronary artery disease (CAD) (n = 15) and ACS (n = 11) contained JUP-81 at more than 2- and 14-fold higher median concentrations, respectively, than plasma of CAD-free individuals (n = 13). In conclusion, this proof of principle study identified and verified JUP isoforms as potential plasma biomarkers for atherosclerosis. Clinical validation studies are needed to determine its diagnostic efficacy and clinical utility as a biomarker for diagnosis, prognosis or monitoring of atherosclerotic vascular diseases

Healthy vascular ageing and early vascular ageing

Chronological age is an important independent predictor of cardiovascular events. Although the cumulative effect of cardiovascular risk factors over time partly explains this relationship, accumulating evidence suggests this is a simplistic interpretation of a more complex concept. With advancing age slowly progressive changes can be seen affecting the structure and function of large and small vessels as well as the phenotype of various cell lines. It is important to note that these changes occur at different rates depending on the clinical context and can be detected much earlier in individuals affected by chronic metabolic or vascular diseases. Determining ‘vascular age’ may therefore be an important tool for cardiovascular risk stratification. This chapter will review the cellular, functional and structural effects of ageing on the vasculature, clinical and research tools for assessing aspects of vascular age, the concept of ‘early vascular ageing’ and associated clinical conditions and pathways to achieve healthy vascular ageing