Journal: bioRxiv
Article Title: Endothelial YAP/TAZ rewiring under cardiometabolic stress drives sex-divergent vascular remodeling in heart failure with preserved ejection fraction
doi: 10.64898/2026.05.07.723127
Figure Lengend Snippet: ( A ) Schematic representation of the microvascular network-on-chip assay adapted from https://aimbiotech.com using https://biorender.com . After three days of vessel self-assembly, the microvessels were treated for another three days with TNF/Glc (TG). ( B ) Representative immunofluorescence pictures of VE-cadherin (green)-stained microvessels (scale-bar, 100µm) under sustained TG treatment showing increased endothelial sprout rupture (white rectangles) particularly when using male HUVECs in combination with human brain pericytes. ( C ) Representative 3D renderings of the segmented vasculogensis-on-chip assay used for quantifications. Single detected objects are colorcoded. ( D ) Quantifications of microvascularity showing surface area and objects counted (fem-EC-derived, red dots, N=14; male-EC-derived, blue dots, N=13). ( E-G ) Gene expression analysis of pericytes after exposure of conditioned medium derived from female (red) or male (blue) ECs showing increase in the inflammatory and fibrotic response, differential TEAD response and sex-specific differences in the expression of NOX4 under TG ( E ). ( F,G ) QRT-PCR analysis of pericytes after exposure of conditioned medium from ECs with silenced YAP/TAZ or with transiently transfected YAP-5SA or TAZ-S89A for CXCL8 ( F ) and PAI1 ( G ). Data represent N=3-8, analyzed from three independent experiments and displayed as mean ± SEM. One-way analysis of variance (ANOVA) followed by multiple-comparisons test. P values < 0.05 (*), <0.005 (**), <0.0005 (***), <0.0001 (****).
Article Snippet: HUVECs from pooled donors (PromoCell; pooled from single-female donors: C-12200, 479Z024, 485Z034, 488Z021, 433Z035.1 ; male-pool: C-12203, 479Z016) and human brain pericytes (ScienCell, Reference: #1200, 27194, single donor) were cultured on 0.2% gelatine precoated dishes/flasks in EGM2-Bulletkit without antibiotics (Lonza, #CC-3156) or in pericyte medium (PM, ScienCell, #1201), respectively.
Techniques: Immunofluorescence, Staining, Derivative Assay, Gene Expression, Expressing, Quantitative RT-PCR, Transfection
