MO56. Upregulation of Left Atrial SLN and CTGF Gene Expression in Porcine Models of Mitral Regurgitation
University of Washington Medical Center
Seattle, WA
United States - Contact Me
Dr. Tomoki Sakata is a Cardiothoracic Transplant and MCS Fellow at the University of Washington Medical Center. He completed his senior residency training in cardiovascular surgery at Chiba University Hospital in Japan, where he also obtained board certification as a cardiovascular surgeon. From 2021 to 2023, he conducted heart failure research at the Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai. He subsequently completed a fellowship in general cardiac surgery at Thomas Jefferson University (2023–2025) and earned his Ph.D. in 2022.
During his residency, Dr. Sakata’s clinical research focused on the tricuspid valve and right ventricular function. In his doctoral studies, he investigated the cardioprotective effects of a specific cytokine on ischemia–reperfusion injury in a donation-after-circulatory-death (DCD) rat model. His translational research interests encompass novel therapeutic strategies for heart failure, including gene therapy, mechanical left ventricular unloading, and donor heart preservation using large-animal models. Clinically, his primary interests lie in 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.