Electrophysiological and structural remodeling of the atria in a mouse model of troponin-i mutation linked hypertrophic cardiomyopathy: Implications for atrial fibrillation
Lim, Wei-Wen, Neo, Melissa, Thanigaimani, Shivshankar, Kuklik, Pawel, Ganesan, Anand N., Lau, Dennis H., Tsoutsman, Tatiana, Kalman, Jonathan M., Semsarian, Christopher, and Saint, David A. (2021) Electrophysiological and structural remodeling of the atria in a mouse model of troponin-i mutation linked hypertrophic cardiomyopathy: Implications for atrial fibrillation. International Journal of Molecular Sciences, 22 (13). 6941.
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Abstract
Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder affecting one in 500 of the general population. Atrial fibrillation (AF) is the most common arrhythmia in patients with HCM. We sought to characterize the atrial electrophysiological and structural substrate in young and aging Gly203Ser cardiac troponin-I transgenic (HCM) mice. At 30 weeks and 50 weeks of age (n = 6 per strain each group), the left atrium was excised and placed on a multi-electrode array (MEA) for electrophysiological study; subsequent histological analyses and plasma samples were analyzed for biomarkers of extracellular matrix remodeling and cell adhesion and inflammation. Wild-type mice of matched ages were included as controls. Young HCM mice demonstrated significantly shortened atrial action potential duration (APD), increased conduction heterogeneity index (CHI), increased myocyte size, and increased interstitial fibrosis without changes in effective refractory periods (ERP), conduction velocity (CV), inflammatory infiltrates, or circulating markers of extracellular matrix remodeling and inflammation. Aging HCM mice demonstrated aggravated changes in atria electrophysiology and structural remodeling as well as increased circulating matrix metalloproteinases (MMP)-2, MMP-3, and VCAM-1 levels. This model of HCM demonstrates an underlying atrial substrate that progresses with age and may in part be responsible for the greater propensity for AF in HCM.
| Item ID: | 73194 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1422-0067 |
| Copyright Information: | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| Date Deposited: | 21 Apr 2022 03:28 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100% |
| SEO Codes: | 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100% |
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