Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction.
edema
heart failure
interstitium
lymphatic
microcirculation
preserved ejection fraction
vascular rarefaction
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
15 12 2020
15 12 2020
Historique:
received:
23
06
2020
revised:
02
10
2020
accepted:
12
10
2020
entrez:
11
12
2020
pubmed:
12
12
2020
medline:
9
3
2021
Statut:
ppublish
Résumé
Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated. This study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na Patients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na Skin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.
Sections du résumé
BACKGROUND
Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated.
OBJECTIVES
This study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na
METHODS
Patients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na
RESULTS
Skin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue
CONCLUSIONS
Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.
Identifiants
pubmed: 33303070
pii: S0735-1097(20)37537-9
doi: 10.1016/j.jacc.2020.10.022
pmc: PMC7724570
pii:
doi:
Substances chimiques
Sodium
9NEZ333N27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2817-2829Subventions
Organisme : British Heart Foundation
ID : RE/13/5/30177
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/6/34217+
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/12/29762
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Author Disclosures This study was supported by British Heart Foundation Centre of Research Excellence Awards to Drs. Touyz, Delles, Petrie, and Rossitto (RE/13/5/30177 and RE/18/6/34217+). Dr. Touyz is supported by a British Heart Foundation Chair award (CH/12/29762). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Références
Circ Res. 2019 May 24;124(11):1598-1617
pubmed: 31120821
Cell Rep. 2018 Oct 16;25(3):571-584.e5
pubmed: 30332639
J Am Coll Cardiol. 2012 Dec 11;60(23):2349-56
pubmed: 23141494
J Am Coll Cardiol. 2011 Jul 12;58(3):265-74
pubmed: 21737017
Eur Heart J. 2017 Feb 14;38(7):478-488
pubmed: 26843279
J Am Soc Nephrol. 2017 Jun;28(6):1867-1876
pubmed: 28154199
Breast Cancer Res Treat. 2009 Oct;117(3):549-57
pubmed: 19052859
Genes Dev. 2011 Oct 15;25(20):2187-97
pubmed: 22012621
Circulation. 2015 Feb 10;131(6):550-9
pubmed: 25552356
J Physiol. 2014 Nov 1;592(21):4697-714
pubmed: 25172950
Circulation. 2003 Jun 10;107(22):2816-22
pubmed: 12756156
Nat Med. 2009 May;15(5):545-52
pubmed: 19412173
Hypertension. 2013 Mar;61(3):635-40
pubmed: 23339169
Circulation. 2016 Apr 12;133(15):1484-97; discussion 1497
pubmed: 26933083
Cell Metab. 2017 Oct 3;26(4):598-609
pubmed: 28844882
Cardiovasc Res. 2015 Jul 1;107(1):89-97
pubmed: 25852084
Circulation. 2018 Jul 3;138(1):12-24
pubmed: 29519849
Cardiovasc Res. 2010 Jul 15;87(2):198-210
pubmed: 20200043
Circ Cardiovasc Imaging. 2019 Apr;12(4):e008074
pubmed: 30943769
Eur Heart J. 2016 Jul 14;37(27):2129-2200
pubmed: 27206819
Front Physiol. 2019 Nov 05;10:1347
pubmed: 31749710
Nat Commun. 2020 Aug 24;11(1):4222
pubmed: 32839436
J Physiol. 1993 May;464:407-22
pubmed: 8229810
Clin Nucl Med. 2012 Jan;37(1):9-13
pubmed: 22157021
Circ Heart Fail. 2015 Mar;8(2):286-94
pubmed: 25344549
Am J Physiol Renal Physiol. 2003 Dec;285(6):F1108-17
pubmed: 12888617
Clin Sci (Lond). 2004 Jun;106(6):627-33
pubmed: 14763898
Cardiovasc Diabetol. 2018 Jan 4;17(1):5
pubmed: 29301520
Eur Surg Res. 2002 Jan-Apr;34(1-2):114-23
pubmed: 11867911
Eur Heart J. 2018 Oct 1;39(37):3439-3450
pubmed: 30165580
Circulation. 2015 Feb 10;131(6):522-4
pubmed: 25552355
J Clin Invest. 2014 Mar;124(3):915-21
pubmed: 24590276
Circulation. 2003 Jul 1;107(25):3129-32
pubmed: 12821539
Circulation. 2018 Mar 20;137(12):e67-e492
pubmed: 29386200
Br J Clin Pharmacol. 2001 Dec;52(6):631-46
pubmed: 11736874
J Am Coll Cardiol. 2013 Jul 23;62(4):263-71
pubmed: 23684677
Am J Physiol Heart Circ Physiol. 2014 May;306(9):H1364-70
pubmed: 24658015
Circulation. 1969 Jun;39(6):723-33
pubmed: 5785287
Circulation. 2006 Nov 14;114(20):2138-47
pubmed: 17088459
J Physiol. 2016 Oct 15;594(20):5749-5768
pubmed: 27219461