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Title: | Dermal Interstitial Alterations in Patients With Heart Failure and Reduced Ejection Fraction A Potential Contributor to Fluid Accumulation? | Authors: | NIJST, Petra Olinevich, Mikhail HILKENS, Petra MARTENS, Pieter DUPONT, Matthias Tang, W. H. Wilson LAMBRICHTS, Ivo NOBEN, Jean-Paul MULLENS, Wilfried |
Issue Date: | 2018 | Publisher: | LIPPINCOTT WILLIAMS & WILKINS | Source: | CIRCULATION-HEART FAILURE, 11(7) (Art N° e004763) | Abstract: | BACKGROUND: Large networks of interstitial glycosaminoglycans help to regulate water and electrolyte homeostasis. The relation between dermal interstitial alterations and occurrence of edema in heart failure patients with reduced ejection fraction (HFrEF) is unknown. We hypothesize that in HFrEF patients (1) interstitial glycosaminoglycan density is increased, (2) changes in the interstitial glycosaminoglycan network are associated with interstitial fluid accumulation, and (3) there is a link between the interstitial glycosaminoglycan network and the renin-angiotensin-aldosterone system. METHODS AND RESULTS: Two punch biopsies of the skin were obtained in healthy subjects (n=18) and HFrEF patients (n=29). Alcian blue staining and immunostaining for the angiotensin II type 1 receptor was performed. After obtaining tissue water content, total interstitial glycosaminoglycan (uronic acid) and sulfated glycosaminoglycan were quantified. A venous blood sample, clinical examination, and echocardiography were obtained. A significantly higher interstitial glycosaminoglycan content was observed in HFrEF patients compared with healthy subjects (uronic acid: 13.0 +/- 4.2 versus 9.6 +/- 1.6 mu g/mg; P=0.002; sulfated glycosaminoglycan: 14.1 [11.7; 18.1] versus 10.0 [9.1; 10.8] mu g/mg; P<0.001). Uronic acid and sulfated glycosaminoglycan density were strongly associated with tissue water content and peripheral edema (uronic acid: rho=0.66; P<0.0001 and sulfated glycosaminoglycan: tau=0.58; P<0.0001). Expression of the angiotensin II type 1 receptor was found on dermal cells, although use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker was associated with significantly lower levels of interstitial glycosaminoglycans in HFrEF patients. CONCLUSIONS: Interstitial glycosaminoglycan concentration is significantly increased in HFrEF patients compared with healthy subjects and correlated with tissue water content and clinical signs of volume overload. A better appreciation of the interstitial compartment might improve management of volume overload in HF. | Notes: | [Nijst, Petra; Martens, Pieter; Dupont, Matthias; Mullens, Wilfried] Ziekenhuis Oost Limburg, Dept Cardiol, Schiepse Bos 6, B-3600 Genk, Belgium. [Nijst, Petra; Hilkens, Petra; Martens, Pieter] Hasselt Univ, Doctoral Sch Med & Life Sci, Diepenbeek, Belgium. [Nijst, Petra; Olinevich, Mikhail; Lambrichts, Ivo; Noben, Jean-Paul; Mullens, Wilfried] Hasselt Univ, Biomed Res Inst, Sch Life Sci, Hasselt, Belgium. [Nijst, Petra; Olinevich, Mikhail; Lambrichts, Ivo; Noben, Jean-Paul; Mullens, Wilfried] Hasselt Univ, Sch Life Sci, Transnat Univ Limburg, Hasselt, Belgium. [Tang, W. H. Wilson] Cleveland Clin, Heart & Vasc Inst, Dept Cardiovasc Med, Cleveland, OH 44106 USA. | Keywords: | heart failure; glycosaminoglycan; homeostasis; edema; sodium;edema; glycosaminoglycan; heart failure; homeostasis; sodium | Document URI: | http://hdl.handle.net/1942/27423 | ISSN: | 1941-3289 | e-ISSN: | 1941-3297 | DOI: | 10.1161/CIRCHEARTFAILURE.117.004763 | ISI #: | 000438926500004 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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