Chromogranin-A production and fragmentation in patients with Takayasu arteritis

Abstract

BackgroundChromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA).MethodsPlasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1–76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling.ResultsLevels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension.ConclusionsThe plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1082-2) contains supplementary material, which is available to authorized users.

Blood Biomarkers for Monitoring and Prognosis of Large Vessel Vasculitides

“…Neoangiogenesis requires a tight modulation of pro- and anti-angiogenic factors which include, among others, full-length chromogranin A (CgA) and its fragment vasostatin-1. Interestingly, the anti-angiogenic potential of these two CgA peptides was found to be reduced in TA patients experiencing progressive arterial remodelling [ 107 ].…”

The Emerging Roles of Chromogranins and Derived Polypeptides in Atherosclerosis, Diabetes, and Coronary Heart Disease

“…Levels of plasma CgA are much higher in patients with dilated cardiomyopathy or hypertrophic cardiomyopathy than the levels in the healthy controls [ 72 ]. Plasma vasostatin-1 levels are increased in patients with Takayasu arteritis [ 73 ]. High levels of secretoneurin are associated with the increased risk of mortality in patients with heart failure, aortic stenosis, or those patients undergoing various cardiac surgeries [ 74 , 75 , 76 ].…”

Radiology and biomarkers in assessing disease activity in Takayasu arteritis

“…Thus, it could provide a safe, non‐invasive means of assessing changes in vascular anatomy over time. It is still a matter of debate whether MRI can add useful information to disease activity assessment with a cross‐sectional, single time‐point assessment of arterial wall edema or post‐contrast enhancement …”