title: The pathophysiological role of interstitial sodium in heart failure.
abstract: The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptoms. Most HF hospitalizations are related to sodium (Na(+)) and fluid retention resulting from neurohumoral up-regulation. Recent insights suggest that Na(+) is not distributed in the body solely as a free cation, but that it is also bound to large interstitial glycosaminoglycan (GAG) networks in different tissues, which have an important regulatory function. In HF, high Na(+) intake and neurohumoral alterations disrupt GAG structure, leading to loss of the interstitial buffer capacity and disproportionate interstitial fluid accumulation. Moreover, a diminished endothelial GAG network (the endothelial glycocalyx) results in increased vascular resistance and disturbed endothelial nitric oxide production. New imaging modalities can help evaluate interstitial Na(+) and endothelial glycocalyx integrity. Furthermore, several therapies have been proven to stabilize interstitial GAG networks. Hence, a better appreciation of this new Na(+) "compartment" might improve current management of HF.
authors: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Petra
authors: P
authors: Nijst
authors: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Frederik H
authors: FH
authors: Verbrugge
authors: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Doctoral School for Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Lars
authors: L
authors: Grieten
authors: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.
authors: Matthias
authors: M
authors: Dupont
authors: Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Paul
authors: P
authors: Steels
authors: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors: W H Wilson
authors: WHW
authors: Tang
authors: Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium; Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium. Electronic address: wilfried.mullens@zol.be.
authors: Wilfried
authors: W
authors: Mullens
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D012964:Sodium / Q000378:metabolism*; D014882:Water-Electrolyte Balance
chemical_list: D006025:Glycosaminoglycans; D012964:Sodium
keywords: endothelial dysfunction; endothelial glycocalyx; glycosaminoglycan; interstitium; proteoglycan