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      Tongguan capsule‐derived herb reduces susceptibility to atrial fibrillation by inhibiting left atrial fibrosis via modulating cardiac fibroblasts

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          Abstract

          Tongguan capsule is a compound Chinese medicine used to treat ischaemic heart diseases. This study aimed to investigate whether Tongguan capsule‐derived herb ( TGD) has a preventive effect on atrial fibrillation ( AF) in post‐myocardial infarction ( MI) rats and to determine the underlying mechanisms. MI was induced by ligation of the left anterior descending coronary artery. TGD was administered to the post‐ MI rats over a 4‐week period. The TGD‐treated rats had lower rates of AF inducibility and shorter AF durations than the MI rats. TGD improved the left atrial ( LA) conduction velocity and homogeneity. It reduced the fibrosis‐positive areas and the protein levels of collagen types I and III in the left atrium. In vitro, it inhibited the expression of collagen types I and III by inhibiting the proliferation, migration, differentiation and cytokine secretion of cardiac fibroblasts ( CFs). In conclusion, the current study demonstrated that TGD reduces susceptibility to AF and improves LA conduction function in rats with post‐ MI by inhibiting left atrial fibrosis and modulating CFs. Targeting the CF population may be a novel antiarrhythmic therapeutic approach.

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          Most cited references47

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          Global epidemiology of atrial fibrillation.

          Atrial fibrillation (AF) is a major public health burden worldwide, and its prevalence is set to increase owing to widespread population ageing, especially in rapidly developing countries such as Brazil, China, India, and Indonesia. Despite the availability of epidemiological data on the prevalence of AF in North America and Western Europe, corresponding data are limited in Africa, Asia, and South America. Moreover, other observations suggest that the prevalence of AF might be underestimated-not only in low-income and middle-income countries, but also in their high-income counterparts. Future studies are required to provide precise estimations of the global AF burden, identify important risk factors in various regions worldwide, and take into consideration regional and ethnic variations in AF. Furthermore, in response to the increasing prevalence of AF, additional resources will need to be allocated globally for prevention and treatment of AF and its associated complications. In this Review, we discuss the available data on the global prevalence, risk factors, management, financial costs, and clinical burden of AF, and highlight the current worldwide inadequacy of its treatment.
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            Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression.

            Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and is associated with increased morbidity and mortality. The incidence of AF is expected to continue to rise with the aging of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then long-standing persistent (chronic or permanent) forms. However, not all patients go through every phase, and the time spent in each can vary widely. Research over the past decades has identified a multitude of pathophysiological processes contributing to the initiation, maintenance, and progression of AF. However, many aspects of AF pathophysiology remain incompletely understood. In this review, we discuss the cellular and molecular electrophysiology of AF initiation, maintenance, and progression, predominantly based on recent data obtained in human tissue and animal models. The central role of Ca(2+)-handling abnormalities in both focal ectopic activity and AF substrate progression is discussed, along with the underlying molecular basis. We also deal with the ionic determinants that govern AF initiation and maintenance, as well as the structural remodeling that stabilizes AF-maintaining re-entrant mechanisms and finally makes the arrhythmia refractory to therapy. In addition, we highlight important gaps in our current understanding, particularly with respect to the translation of these concepts to the clinical setting. Ultimately, a comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.
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              Fibroblasts and myofibroblasts: what are we talking about?

              Cardiac myocytes, although large enough to make up most of the heart volume, are only a minority of cells within the heart with fibroblasts and blood vessel components (endothelial and smooth muscle cells) making up the remainder of the heart. In recent years, there has been increasing interest in the nonmyocyte population within the heart. This is attributable, in part, to our increasing understanding of the biology of the nonmyocyte cell types and additionally it is the result of our awakening realization that these cells are not static but rather that they are dynamic in nature indicating that they play a more active role in cardiac function than previously imagined. Studies now show that fibroblasts are involved in formation of the extracellular matrix and they control the size of the extracellular matrix. Additionally, they participate in the repair process by differentiating into myofibroblasts, which are cells involved in the inflammatory response to injury. Myofibroblasts migrate to the sites of injury where they produce cytokines, thus enhancing the inflammatory response. This review discusses both structural and functional differences between the two cell types and examines the different roles of these two different cell types in the heart.
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                Author and article information

                Contributors
                minzhouzhang@aliyun.com
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                19 November 2018
                February 2019
                : 23
                : 2 ( doiID: 10.1111/jcmm.2019.23.issue-2 )
                : 1197-1210
                Affiliations
                [ 1 ] Department of Critical‐care Medicine Guangdong Provincial Hospital of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China
                [ 2 ] Guangzhou Key Laboratory of Myocardial Infarction in Chinese Medical Prevention and Treatment Guangzhou China
                [ 3 ] Cardiac Electrophysiology Research Team Guangdong Provincial Hospital of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China
                [ 4 ] New Patent Chinese Medicine and Decoction Pieces Innovative Research and Development Team The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine Guangzhou China
                Author notes
                [*] [* ] Correspondence

                Minzhou Zhang, Department of Critical‐care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

                Email: minzhouzhang@ 123456aliyun.com

                Author information
                http://orcid.org/0000-0002-2075-5641
                Article
                JCMM14022
                10.1111/jcmm.14022
                6349173
                30456908
                abc8cb2c-6ebb-4024-923b-ef8fb4bd8b9b
                © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 August 2018
                : 11 October 2018
                : 16 October 2018
                Page count
                Figures: 7, Tables: 1, Pages: 14, Words: 7445
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81503394
                Funded by: Guangzhou Science and Technology Foundation
                Award ID: 201607010364
                Award ID: 2014A020221026
                Funded by: Natural Science Foundation of Guangdong Province
                Award ID: 2015A030313354
                Award ID: 2016A030313634
                Award ID: 2017A030313888
                Funded by: Guangdong Provincial New Chinese Medicine Research and Development Project in 2015
                Funded by: The Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine
                Award ID: YN2018MJ02
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                jcmm14022
                February 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.5.6 mode:remove_FC converted:28.01.2019

                Molecular medicine
                atrial fibrillation,atrium,chinese medicine,fibroblasts,fibrosis
                Molecular medicine
                atrial fibrillation, atrium, chinese medicine, fibroblasts, fibrosis

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