The urinary proteomic profile of fibromuscular dysplasia.

Abstract

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory arterial disease of unclear origin, that may affect virtually all middle-sized arteries, mostly found in young or middle-aged women. More than half of patients have lesions in two or more arterial beds. While many cases are asymptomatic or associated with aspecific symptoms (mild hypertension, migraines, tinnitus), a number of patients develop severe complications such as resistant hypertension, carotid dissection, early stroke or mesenteric ischemia. Two subtypes of FMD have been described: focal and multifocal FMD. Focal FMD, characterized by a focal arterial stenosis of variable length is often difficult to differentiate from localized atherosclerosis, inflammatory or genetic arterial diseases. The hallmark of multifocal FMD, the so-called string of beads, is considered as almost pathognomonic. However, besides classical forms, many patients harbour less typical lesions such as presence of one or two non-circumferential beads, mild irregularities or less regular successive enlargements of arteries. Furthermore, lesions indistinguishable from string of beads are often found in extra-coronary arteries of patients who underwent a spontaneous coronary artery dissection (SCAD), leading some authors to consider SCAD as a form of FMD. Finally, a substantial proportion of patients with FMD harbour arterial aneurysms or dissections, and patients with such complications are sometimes considered to have atypical FMD, even in the absence of a string of beads or focal stenosis. In view of these elements, the development and validation of biomarkers, and particular proteomic biomarkers is of interest to unravel the pathophysiology, to facilitate diagnosis, improve classification and predict complications and evolution of FMD, SCAD and related diseases. Urinary proteomics appears as particularly promising in view of the predominantly renovascular expression of FMD, and of previous identification of proteomic signatures associated with both renal and cardiovascular diseases. In a recent pilot study, we have described a urinary proteomic classifier that allowed distinguishing with high accuracy patients with (mostly renal, multifocal) FMD, both from healthy controls and from patients with chronic kidney diseases and coronary heart disease. This classifier includes mostly collagen-derived peptides, which may suggest increased collagen turnover in affected arteries. The objectives of this presentation are to describe urinary proteomic profile associated with primary FMD, to report preliminary results obtained in patients with SCAD associated with FMD or not, and to discuss the potential consequences of such findings for the understanding, diagnosis and classification of these overlapping entities.