1. The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin
- Author
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A. Mark Richards, Philippe Bizouarn, Pierre-Olivier Ludes, David M. Smadja, Alain Cohen-Solal, Jagmeet P. Singh, Chris J. Pemberton, Nicolas Vodovar, Bernard Cholley, Alexandre Mebazaa, Julien Pottecher, Pamela Ballan, Malha Sadoune, Nicolas Gendron, Jane-Lise Samuel, Hélène Nougué, Jackie Szymonifka, Quynh A. Truong, Jean-Marie Launay, Mattia Arrigo, Christian Latremouille, and Alain Carpentier
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Systole ,Heart, Artificial ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Natriuretic Peptide, Brain ,medicine ,Natriuretic peptide ,Humans ,030212 general & internal medicine ,Postoperative Period ,RNA, Messenger ,Natriuretic Peptides ,Neprilysin ,Coronary sinus ,Geographic difference ,Aged ,Heart Failure ,business.industry ,Heart ,Venous blood ,Middle Aged ,medicine.disease ,Brain natriuretic peptide ,Peptide Fragments ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Signal Transduction - Abstract
Aims Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P Conclusion The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.
- Published
- 2017