MO56. Upregulation of Left Atrial SLN and CTGF Gene Expression in Porcine Models of Mitral Regurgitation
Thomas Jefferson University Hospital
Philadelphia, PA
United States - Contact Me
Dr. Sakata is a cardiac surgery fellow at Thomas Jefferson University Hospital. After completing the senior residency training in cardiovascular surgery at Chiba University Hospital (Japan) and acquiring Japanese board certification for cardiovascular surgeon, he was engaged in heart failure research at Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai from 2021 to 2023. He also acquired PhD in 2022. He had been engaged in clinical research regarding the tricuspid valve and right ventricular function throughout the residency period. During postgraduate course, he also investigated cardioprotective effect of a specific cytokine on ischemia/reperfusion injury in donation- after-circulatory-death rat model. His translational research interest includes various heart failure treatment including gene therapy, mechanical LV unloading and donor heart preservation using large animal models. His clinical research focuses on mitral valve surgery, mechanical circulatory support and heart transplantation.
Description
Methods: Eighteen Yorkshire pigs (all female, 37.6±5.4 kg) were enrolled in this study. MR was induced in 13 Yorkshire pigs using catheter-based procedures. Six pigs underwent simultaneous occlusions of the left circumflex artery and the diagonal branch, which resulted in ischemic MR (IMR group) due to bulging of the left ventricular (LV) lateral wall. The other seven pigs underwent chordal severing to induce leaflet prolapse simulating degenerative MR (DMR group). Three months after model creation, animals were sacrificed and the expression of SLN and CTGF in LA was assessed with quantitative PCR. Five normal pigs underwent the same assessment (Sham group).
Results: Echocardiography showed that LV end-diastolic and end-systolic volume indexes, maximum and minimum LA volume indexes were significantly larger in the IMR group than the other two groups. LV ejection fraction, longitudinal and circumferential strain, LA emptying function and reservoir strain were significantly impaired in the IMR group than the other two groups. LA SLN and CTGF expressions were both significantly upregulated in the IMR group compared to the Sham group, and had significant correlation with LA reservoir strain and LV end-diastolic volume index, respectively (Figure). The DMR group showed the same trends in echocardiographic and gene expression data as the IMR group, while there was no statistical significance compared to the Sham group.
Conclusions: Ischemic MR resulted in an exaggerated LA remodeling with significant upregulation of SLN and CTGF in the LA. These genes might serve as possible therapeutic targets for LA remodeling.