Galectin-3 in Peripheral Artery Disease. Relationships with Markers of Oxidative Stress and Inflammation.

Isabel Fort-Gallifa,Josep Simó,Jordi Camps,Vicente Martín-Paredero,Anabel García-Heredia,Noemí Cabré,Fedra Luciano-Mateo,Anna Hernández-Aguilera,Jorge Joven

doi:10.3390/ijms18050973

Abstract

Galectin-3 is a modulator of oxidative stress, inflammation, and fibrogenesis involved in the pathogenesis of vascular diseases. The present study sought to characterize, in patients with peripheral artery disease (PAD), the localization of galectin-3 in arterial tissue, and to analyze the relationships between the circulating levels of galectin-3 and oxidative stress and inflammation. It also sought to compare the diagnostic accuracy of galectin-3 with that of other biochemical markers of this disease. We analyzed femoral or popliteal arteries from 50 PAD patients, and four control arteries. Plasma from 86 patients was compared with that from 72 control subjects. We observed differences in the expression of galectin-3 in normal arteries, and arteries from patients with PAD, with a displacement of the expression from the adventitia to the media, and the intima. In addition, plasma galectin-3 concentration was increased in PAD patients, and correlated with serologic markers of oxidative stress (F2-isoprostanes), and inflammation [chemokine (C−C motif) ligand 2, C-reactive protein, β-2-microglobulin]. We conclude that the determination of galectin-3 has good diagnostic accuracy in the assessment of PAD and compares well with other analytical parameters currently in use.

Highlights

Galectins are a lectin family able to bind to β-galactoside groups [1]
We recently reported that the measurement of the serum concentrations of F2-isoprostanes and/or the chemokine (C−C motif) ligand 2 (CCL2), markers of oxidative stress and inflammation, may constitute excellent biomarkers for the diagnosis of peripheral artery disease (PAD) [27]
Galectin-3 expression was evenly distributed throughout the adventitia of the artery wall

Summary

Introduction

To-date, 14 mammalian galectins have been identified, all of which contain a carbohydrate-recognition-binding domain of 130 amino acids. Galectin-3 is a 29- to 35-kDa protein consisting of two domains, the C-terminal carbohydrate recognition binding domain, and the N-terminal domain that has a unique short end continuing into a Pro-Gly-Ala-Tyr-rich repeat motif [2]. Inactivation of galectin-3 gene or therapeutic modulation of the protein levels was shown to halt the progression of cardiac remodeling, attenuate myocardial fibrogenesis, reduce the atherosclerotic lesion size, and preserve ventricular function in rats and mice [12,13,14,15]. Galectin-3 is involved in vascular smooth muscle cell osteogenic differentiation [16], myocardial fibrosis and inflammation [17], together with a strong suggestion of association with the risk of cardiac fibrosis, hearth failure, and mortality in the general population, and in patients with atherosclerosis [7,18,19,20]

Methods

Results

Discussion

Conclusion