Fenotipos de válvula aórtica bicúspide y dilatación de aorta ascendente : estudio mediante cardiorresonancia

El objetivo del estudio ha sido caracterizar mediante cardiorresonancia los fenotipos de válvula aórtica bicúspide (VAB) y su asociación con patrones de dilatación de aorta ascendente (AA). En este estudio la VAB fenotipo 1 (fusión velo coronario derecho -izquierdo) es la más prevalente y se asocia a coartación aórtica, insuficiencia aórtica moderada-severa y dilatación de raiz aórtica. El fenotipo 2 de VAB (fusión velo coronario derecho- no coronario) se asocia a dilatación de porción tubular aórtica. La edad predice dilatación de AA en pacientes con VAB y la estenosis aórtica moderada-severa es un factor protector contra dicha dilatación.L'objectiu de l'estudi ha estat caracteritzar mitjançant ressonància magnètica nuclear cardíaca els fenotips de vàlvula aòrtica bicúspide (VAB) i la seva associació amb patrons de dilatació d'aorta ascendent (AA). En aquest estudi la VAB fenotip 1 (fusió valva coronàrica dreta -esquerra) és la més prevalent i s'associa a coartació aòrtica, insuficiència aòrtica moderada- greu i dilatació d'arrel aòrtica. El fenotip 2 de VAB (fusió valva coronàrica dreta- no coronàrica) s'associa a dilatació de porció tubular aòrtica. L'edat prediu dilatació de AA en pacients amb VAB i l'estenosi aòrtica moderada- greu és un factor protector contra aquesta dilatació

Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium : systems biology study

Altres ajuts: This work was supported by the Spanish Cardiovascular Network of Cell Therapy (Red TerCel RD16/0011/018) and Ciber CV(CB16/11/00411) from the Instituto Salud Carlos III (to LB). Additional funding was received from Plan Nacional de Salud (PNS SAF2016-76819-R to LB, 2015-71653-R to GV) from the Spanish Ministry of Science and Innovation and FEDER funds; from Instituto de Salud Carlos III (CPII13/00012 to GA); and support from a grant from the Muy Ilustrísima Administración from the Hospital de la Santa Creu I Sant Pau (to MG). The authors thank Fundacion Jesus Serra, Barcelona for continuous support.Myocardial microvascular loss after myocardial infarction (MI) remains a therapeutic challenge. Autologous stem cell therapy was considered as an alternative; however, it has shown modest benefits due to the impairing effects of cardiovascular risk factors on stem cells. Allogenic adipose-derived stem cells (ASCs) may overcome such limitations, and because of their low immunogenicity and paracrine potential may be good candidates for cell therapy. In the present study we investigated the effects of allogenic ASCs and their released products on cardiac rarefaction post MI. Pig subcutaneous adipose tissue ASCs were isolated, expanded and GFP-labeled. ASC angiogenic function was assessed by the in-vivo chick chorioallantoic membrane (CAM) model. Pigs underwent MI induction and 7 days after were randomized to receive: allogenic ASCs (intracoronary infusion); conditioned media (CM; intravenous infusion); ASCs + CM; or PBS/placebo (control). Cardiac damage and function were monitored by 3-T cardiac magnetic resonance imaging upon infusion (baseline CMR) and 1 and 3 weeks thereafter. We assessed in the myocardium: microvessel density; angiogenic markers (CD105, CD31, TF, VEGFR2, VEGFR1, vWF, eNOS, CD62); collagen deposition; and reparative fibrosis (TGFβ/TβRII/collagen). Differential proteomics of ASCs and CM was performed to characterize the ASC protein signature. CAM indicated a significant ASC proangiogenic capacity. In pigs after MI, only PBS/placebo animals displayed an impaired cardiac function 3 weeks after infusion (p < 0.05 vs baseline). Administration of ASCs + CM significantly enhanced neovessel formation and favored cardiac repair post MI (p < 0.05 vs the other groups). Molecular markers of angiogenesis were significantly upregulated both at transcriptional and protein levels (p < 0.05). The in-silico bioinformatics analysis of the ASC and CM proteome (interactome) indicated activation of a coordinated protein network involved in the formation of microvessels and the resolution of rarefaction. Coadministration of allogenic ASCs and their CM synergistically contribute to the neovascularization of the infarcted myocardium through a coordinated upregulation of the proangiogenic protein interactome. The online version of this article (doi:10.1186/s13287-017-0509-2) contains supplementary material, which is available to authorized users