Autoregulation of Pulsatile Bioprosthetic Total Artificial Heart is Involved in Endothelial Homeostasis Preservation

Abstract

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3–6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values (p = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found (p = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.

Keywords

bioprosthetic total artificial heart - biomarker - endothelial - sEPCR - sEndoglin - endothelial progenitors - ECFC

Authors' Contributions

D.M.S. supervised the work, analyzed the data, and wrote the paper. R.C. analyzed the data and performed statistical analysis. E.R. and L.M. performed and analyzed ECFC in vitro assays. B.P., C.P., N.G., and J.R. performed analysis and analyzed data. C.G. performed analysis, analyzed data, and wrote the paper. Y.P., M.B., J.C.R., M.K., P.I., C.L., and I.N. included patients and reviewed the paper. C.L. and I.N. are principal investigator, respectively, of feasibility and pivotal study. C.G. and P.G. analyzed the data and reviewed the paper. A.C., J.C.P., and P.J. organized clinical trials. A.C. is inventor of C-TAH and reviewed the paper.

Publikationsverlauf

Eingereicht: 02. Januar 2020

Angenommen: 18. Mai 2020

Artikel online veröffentlicht:
20. Juli 2020

• References

• 1 Smadja DM, Saubaméa B, Susen S. , et al. Bioprosthetic total artificial heart induces a profile of acquired hemocompatibility with membranes recellularization. J Am Coll Cardiol 2017; 70 (03) 404-406
• 2 Smadja DM, Susen S, Rauch A. , et al. The Carmat bioprosthetic total artificial heart is associated with early hemostatic recovery and no acquired von Willebrand syndrome in calves. J Cardiothorac Vasc Anesth 2017; 31 (05) 1595-1602
• 3 Latrémouille C, Carpentier A, Leprince P. , et al. A bioprosthetic total artificial heart for end-stage heart failure: results from a pilot study. J Heart Lung Transplant 2018; 37 (01) 33-37
• 4 Richez U, De Castilla H, Guerin CL. , et al. Hemocompatibility and safety of the Carmat total artificial heart hybrid membrane. Heliyon 2019; 5 (12) e02914
• 5 Bizouarn P, Roussel JC, Trochu JN, Perlès JC, Latrémouille C. Effects of pre-load variations on hemodynamic parameters with a pulsatile autoregulated artificial heart during the early post-operative period. J Heart Lung Transplant 2018; 37 (01) 161-163
• 6 Rodrigo GC, Herbert KE. Regulation of vascular function and blood pressure by circadian variation in redox signalling. Free Radic Biol Med 2018; 119: 115-120
• 7 Silvestre JS, Smadja DM, Lévy BI. Postischemic revascularization: from cellular and molecular mechanisms to clinical applications. Physiol Rev 2013; 93 (04) 1743-1802
• 8 Hoefer IE, den Adel B, Daemen MJ. Biomechanical factors as triggers of vascular growth. Cardiovasc Res 2013; 99 (02) 276-283
• 9 Rossi E, Poirault-Chassac S, Bieche I. , et al. Human endothelial colony forming cells express intracellular CD133 that modulates their vasculogenic properties. Stem Cell Rev Rep 2019; 15 (04) 590-600
• 10 Nevo N, Lecourt S, Bièche I. , et al. Valproic acid decreases endothelial colony forming cells differentiation and induces endothelial-to-mesenchymal transition-like process. Stem Cell Rev Rep 2020; 16 (02) 357-368
• 11 d'Audigier C, Susen S, Blandinieres A. , et al. Egfl7 represses the vasculogenic potential of human endothelial progenitor cells. Stem Cell Rev Rep 2018; 14 (01) 82-91
• 12 Smadja DM, Melero-Martin JM, Eikenboom J, Bowman M, Sabatier F, Randi AM. Standardization of methods to quantify and culture endothelial colony-forming cells derived from peripheral blood: position paper from the International Society on Thrombosis and Haemostasis SSC. J Thromb Haemost 2019; 17 (07) 1190-1194
• 13 Delafont B, Carroll K, Vilain C, Pham E. Investigation of mixed model repeated measures analyses and non-linear random coefficient models in the context of long-term efficacy data. Pharm Stat 2018; 17 (05) 515-526
• 14 Edwards LJ. Modern statistical techniques for the analysis of longitudinal data in biomedical research. Pediatr Pulmonol 2000; 30 (04) 330-344
• 15 Carpentier A, Latrémouille C, Cholley B. , et al. First clinical use of a bioprosthetic total artificial heart: report of two cases. Lancet 2015; 386 (10003): 1556-1563
• 16 Kang J, Hennessy-Strahs S, Kwiatkowski P. , et al. Continuous-flow LVAD support causes a distinct form of intestinal angiodysplasia. Circ Res 2017; 121 (08) 963-969
• 17 Randi AM, Smith KE, Castaman G. von Willebrand factor regulation of blood vessel formation. Blood 2018; 132 (02) 132-140
• 18 Tabit CE, Chen P, Kim GH. , et al. Elevated angiopoietin-2 level in patients with continuous-flow left ventricular assist devices leads to altered angiogenesis and is associated with higher nonsurgical bleeding. Circulation 2016; 134 (02) 141-152
• 19 Vincent F, Rauch A, Loobuyck V. , et al. Arterial pulsatility and circulating von Willebrand factor in patients on mechanical circulatory support. J Am Coll Cardiol 2018; 71 (19) 2106-2118
• 20 Tabit CE, Coplan MJ, Chen P, Jeevanandam V, Uriel N, Liao JK. Tumor necrosis factor-alpha levels and non-surgical bleeding in continuous-flow left ventricular assist devices. J Heart Lung Transplant 2018; 37 (01) 107-115
• 21 Mancini D, Monteagudo J, Suárez-Fariñas M. , et al. New methodologies to accurately assess circulating active transforming growth factor-β1 levels: implications for evaluating heart failure and the impact of left ventricular assist devices. Transl Res 2018; 192: 15-29
• 22 Bank AJ, Lee PC, Kubo SH. Endothelial dysfunction in patients with heart failure: relationship to disease severity. J Card Fail 2000; 6 (01) 29-36
• 23 Anderson CE, Hamm LL, Batuman G. , et al. The association of angiogenic factors and chronic kidney disease. BMC Nephrol 2018; 19 (01) 117
• 24 Mansour SG, Zhang WR, Moledina DG. , et al; TRIBE-AKI Consortium. The association of angiogenesis markers with acute kidney injury and mortality after cardiac surgery. Am J Kidney Dis 2019; 74 (01) 36-46
• 25 Oberleithner H, Riethmüller C, Schillers H, MacGregor GA, de Wardener HE, Hausberg M. Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc Natl Acad Sci U S A 2007; 104 (41) 16281-16286
• 26 Arrigo M, Vodovar N, Nougué H. , et al. The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin. Eur Heart J 2018; 39 (20) 1794-1798
• 27 Qu D, Wang Y, Esmon NL, Esmon CT. Regulated endothelial protein C receptor shedding is mediated by tumor necrosis factor-alpha converting enzyme/ADAM17. J Thromb Haemost 2007; 5 (02) 395-402
• 28 Lécuyer H, Virion Z, Barnier JP. , et al. An ADAM-10 dependent EPCR shedding links meningococcal interaction with endothelial cells to purpura fulminans. PLoS Pathog 2018; 14 (04) e1006981
• 29 Zaghloul A, Al-Bukhari TA, Al-Pakistani HA. , et al. Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: their role in the prediction of vascular complications. Diabetes Res Clin Pract 2014; 106 (03) 597-604
• 30 Saposnik B, Peynaud-Debayle E, Stepanian A. , et al. Elevated soluble endothelial cell protein C receptor (sEPCR) levels in women with preeclampsia: a marker of endothelial activation/damage?. Thromb Res 2012; 129 (02) 152-157
• 31 Rossi E, Bernabeu C, Smadja DM. Endoglin as an adhesion molecule in mature and progenitor endothelial cells: a function beyond TGF-β. Front Med (Lausanne) 2019; 6: 10
• 32 Valbuena-Diez AC, Blanco FJ, Oujo B. , et al. Oxysterol-induced soluble endoglin release and its involvement in hypertension. Circulation 2012; 126 (22) 2612-2624
• 33 Aristorena M, Gallardo-Vara E, Vicen M. , et al. MMP-12, secreted by pro-inflammatory macrophages, targets endoglin in human macrophages and endothelial cells. Int J Mol Sci 2019; 20 (12) 20
• 34 Venkatesha S, Toporsian M, Lam C. , et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006; 12 (06) 642-649
• 35 Rossi E, Smadja DM, Boscolo E. , et al. Endoglin regulates mural cell adhesion in the circulatory system. Cell Mol Life Sci 2016; 73 (08) 1715-1739
• 36 Jacob MP, Cazaubon M, Scemama A. , et al. Plasma matrix metalloproteinase-9 as a marker of blood stasis in varicose veins. Circulation 2002; 106 (05) 535-538
• 37 Smadja DM. Bone marrow very small embryonic-like stem cells: new generation of autologous cell therapy soon ready for prime time?. Stem Cell Rev Rep 2017; 13 (02) 198-201
• 38 Guerin CL, Loyer X, Vilar J. , et al. Bone-marrow-derived very small embryonic-like stem cells in patients with critical leg ischaemia: evidence of vasculogenic potential. Thromb Haemost 2015; 113 (05) 1084-1094