Sandel, D. | bioRxiv Science

bioRxiv2026

Effect of Clover versus Zipping on Annular Geometry and Dynamics in Tricuspid Edge-to-Edge Repair

Introduction: Transcatheter edge-to-edge repair effectively reduces tricuspid regurgitation (TR), with some patients showing an additional 'annuloplasty effect'. Methods: Ten adult sheep underwent pulmonary artery banding to induce right ventricular failure and functional TR. Six weeks later, sonomicrometry crystals were implanted around the tricuspid annulus (TA). Two Abbott XTW clips were then placed using either a Zipping (n=5) or Clover (n=5) configuration. Echocardiographic and sonomicrometry data were collected before and after clip implantation to assess TA geometry and function. Results: The model produced right ventricular dilation, dysfunction, and moderate-to-severe functional TR. In all animals, leaflet approximation with two clips significantly reduced TR severity (3.6+/-0.5 to 1.3+/-1.1; p=0.01) and septal-lateral annular diameter (29.2+/-2.2 to 26.7+/-2.9 mm; p=0.01). However, a significant reduction in septal-lateral annular diameter occurred only with the Clover technique (30+/-2 to 27+/-1 mm; p=0.001). Conclusions: Both techniques reduced TR, but only the Clover configuration produced an acute annuloplasty effect by selectively decreasing septal-lateral annular diameter.

bioengineering↗

bioRxiv2021

Deciphering the tumor-specific immunopeptidome in vivo with genetically engineered mouse models

Effective immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex Class I (MHC-I). Recent developments in proteomics have improved the identification of peptides that are naturally presented by MHC-I, collectively known as the "immunopeptidome". Current approaches to profile tumor immunopeptidomes have been limited to in vitro investigation, which fails to capture the in vivo repertoire of MHC-I peptides, or bulk tumor lysates, which are obscured by the lack of tumor-specific MHC-I isolation. To overcome these limitations, we report here the engineering of a Cre recombinase-inducible affinity tag into the endogenous mouse MHC-I gene and targeting of this allele to the KrasLSL-G12D/+; p53fl/fl (KP) mouse model (KP; KbStrep). This novel approach has allowed us to isolate tumor-specific MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LUAD) in vivo. With this powerful analytical tool, we were able to profile the evolution of the LUAD immunopeptidome through tumor progression and show that in vivo MHC-I presentation is shaped by post-translational mechanisms. We also uncovered novel, putative LUAD tumor associated antigens (TAAs). Many peptides that were recurrently presented in vivo exhibited very low expression of the cognate mRNA, provoking reconsideration of antigen prediction pipelines that triage peptides according to transcript abundance. Beyond cancer, the KbStrep allele is compatible with a broad range of Cre-driver lines to explore antigen presentation in vivo in the pursuit of understanding basic immunology, infectious disease, and autoimmunity.

cancer biology↗