Upregulation of Left Atrial SLN and CTGF Gene Expression in Porcine Models of Mitral Regurgitation
Presented During:
Friday, May 5, 2023: 7:00AM - 7:05AM
New York Hilton Midtown
Posted Room Name:
Petit Trianon
Abstract No:
MO056
Submission Type:
Abstract Submission
Authors:
Tomoki Sakata (1), Renata Mazurek (1), Spyros Mavropoulos (1), Anjali Ravichandran (1), Jonas Marx (1), Kiyotake Ishikawa (1)
Institutions:
(1) Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Submitting Author:
Tomoki Sakata
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Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Co-Author(s):
Renata Mazurek
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Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Spyros Mavropoulos
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Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Anjali Ravichandran
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Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Jonas Marx
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Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Kiyotake Ishikawa
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Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai
Presenting Author:
Tomoki Sakata
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Funabashi Municipal Medical Center
Funabashi Municipal Medical Center
Abstract:
Objective: Sarcolipin (SLN) is a regulator of the atrial sarcoplasmic reticulum Ca2+-ATPase, and Connective Tissue Growth Factor (CTGF) is a promoter of myocardial remodeling. Their expression in the diseased left atrium (LA) remains unclearly defined. The aim of this study was to evaluate their involvement in LA remodeling in porcine models of mitral regurgitation (MR).
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.
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.
Mitral Conclave:
From Bench to Bedside: Mitral Valve Research
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