Mitchel R Stacy1, Ben A Lin1, Stephanie L Thorn1, David C Lobb2, Mark W Maxfield1, Craig Novack2, Kia N Zellars2, Lisa Freeburg2, Joseph G Akar1, Albert J Sinusas3, Francis G Spinale4. 1. Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. 2. Cell Biology & Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina. 3. Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut. 4. Cell Biology & Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina; Columbia VA Health Care System, Columbia, South Carolina. Electronic address: cvctrc@uscmed.sc.edu.
Abstract
BACKGROUND: Left ventricular (LV) remodeling following a myocardial infarction (MI) is associated with new-onset atrial fibrillation (AF). LV remodeling post-MI is characterized by regional changes in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), causing extracellular matrix (ECM) remodeling. OBJECTIVE: The purpose of this study was to test the hypothesis that a shift in regional atrial MMP activity, MMP/TIMP expression, and ECM remodeling occurs post-MI, which cause increased vulnerability to AF. METHODS: MI was induced in pigs (weight 25 kg; coronary ligation; n = 9). At approximately 14 days post-MI, an atrial electrical stimulation protocol was performed, after which an MMP radiotracer was infused, MMP/TIMP mRNA profiling performed, and ECM collagen assessed by histochemistry. An additional 7 non-MI pigs served as controls. RESULTS: AF could be induced in 89% (8/9) of the post-MI pigs but none of the controls. MMP activity (MMP radiotracer uptake) increased by approximately 2-fold in most atrial regions post-MI, whereas fibrillar collagen content was unchanged or actually reduced in right atrial regions and increased in left atrial regions. MMP/TIMP profiles revealed a heterogeneous pattern from the left atrial appendage to right atrial regions. CONCLUSION: AF vulnerability early post-MI was associated with a heterogeneous pattern of atrial ECM remodeling, detectable by noninvasive molecular imaging. Detection of early atrial MMP activation post-MI may help define the myocardial substrate underlying AF.
BACKGROUND: Left ventricular (LV) remodeling following a myocardial infarction (MI) is associated with new-onset atrial fibrillation (AF). LV remodeling post-MI is characterized by regional changes in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), causing extracellular matrix (ECM) remodeling. OBJECTIVE: The purpose of this study was to test the hypothesis that a shift in regional atrial MMP activity, MMP/TIMP expression, and ECM remodeling occurs post-MI, which cause increased vulnerability to AF. METHODS: MI was induced in pigs (weight 25 kg; coronary ligation; n = 9). At approximately 14 days post-MI, an atrial electrical stimulation protocol was performed, after which an MMP radiotracer was infused, MMP/TIMP mRNA profiling performed, and ECM collagen assessed by histochemistry. An additional 7 non-MI pigs served as controls. RESULTS: AF could be induced in 89% (8/9) of the post-MI pigs but none of the controls. MMP activity (MMP radiotracer uptake) increased by approximately 2-fold in most atrial regions post-MI, whereas fibrillar collagen content was unchanged or actually reduced in right atrial regions and increased in left atrial regions. MMP/TIMP profiles revealed a heterogeneous pattern from the left atrial appendage to right atrial regions. CONCLUSION: AF vulnerability early post-MI was associated with a heterogeneous pattern of atrial ECM remodeling, detectable by noninvasive molecular imaging. Detection of early atrial MMP activation post-MI may help define the myocardial substrate underlying AF.
Authors: Irfan M Khurram; Mohammadali Habibi; Esra Gucuk Ipek; Jonathan Chrispin; Eunice Yang; Kotaro Fukumoto; Jane Dewire; David D Spragg; Joseph E Marine; Ronald D Berger; Hiroshi Ashikaga; Jack Rickard; Yiyi Zhang; Vadim Zipunnikov; Stefan L Zimmerman; Hugh Calkins; Saman Nazarian Journal: JACC Cardiovasc Imaging Date: 2016-01-06
Authors: Sebastian Clauss; Dominik Schüttler; Christina Bleyer; Julia Vlcek; Mehdi Shakarami; Philipp Tomsits; Sarah Schneider; Florian Maderspacher; Kavi Chataut; Anna Trebo; Christine Wang; Jan Kleeberger; Ruibing Xia; Elisabeth Baloch; Bianca Hildebrand; Steffen Massberg; Reza Wakili; Stefan Kääb Journal: PLoS One Date: 2020-05-04 Impact factor: 3.240