Abstract

BackgroundFibulin-1 is one of a few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease.MethodsPlasma fibulin-1 was determined in subjects with chronic kidney disease (n = 32; median age 62.5, inter-quartile range 51 – 73 years) and 60 age-matched control subjects. Among kidney disease patients serological biomarkers related to cardiovascular disease (fibrinogen, interleukin 6, C-reactive protein) were measured. Arterial applanation tonometry was used to determine central hemodynamic and arterial stiffness indices.ResultsWe observed a positive correlation of fibulin-1 levels with age (r = 0.38; p = 0.033), glycated hemoglobin (r = 0.80; p = 0.003), creatinine (r = 0.35; p = 0.045), and fibrinogen (r = 0.39; p = 0.027). Glomerular filtration rate and fibulin-1 were inversely correlated (r = −0.57; p = 0.022). There was a positive correlation between fibulin-1 and central pulse pressure (r = 0.44; p = 0.011) and central augmentation pressure (r = 0.55; p = 0.001). In a multivariable regression model, diabetes, creatinine, fibrinogen and central augmentation pressure were independent predictors of plasma fibulin-1.ConclusionIncreased plasma fibulin-1 levels were associated with diabetes and impaired kidney function. Furthermore, fibulin-1 levels were associated with hemodynamic cardiovascular risk markers. Fibulin-1 is a candidate in the pathogenesis of cardiovascular disease observed in chronic kidney disease and diabetes.

Highlights

  • Fibulin-1 is one of a few extracellular matrix proteins present in blood in high concentrations

  • We observed significantly increased fibulin-1 concentrations in patients with chronic kidney disease plus diabetes mellitus compared to patients with chronic kidney disease without diabetes mellitus

  • In the present study we show a positive association between plasma fibulin-1 concentration and several cardiovascular risk markers in patients with Chronic kidney disease (CKD)

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Summary

Introduction

Fibulin-1 is one of a few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease. The extracellular matrix protein fibulin-1 is emerging as a new factor in cardiovascular disease. The plasma concentration of fibulin-1 is a predictor of all cause and cardiovascular mortality in patients with diabetes mellitus [1]. Fibulin-1 belongs to a family of extracellular matrix (ECM) proteins with functional associations with elastic fibers and basement membranes. Fibulin-1 interacts with a number of ECM molecules, but whether it serves a structural role has not yet been established [2]. Fibulin-1 is expressed in embryonic and adult vascular smooth muscle cells (VSMC) [3,4].

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