PMC:6019327 / 41478-44424
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6019327","sourcedb":"PMC","sourceid":"6019327","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6019327","text":"AF-Related Extracellular Matrix Remodeling\nPersistent AF itself leads to electrical remodeling and fibrosis of the atria.157,158 Experimental and clinical data point to a complex pathophysiology involving diverse factors, including oxidative stress, calcium overload, atrial dilatation, microRNAs, inflammation, and myofibroblast activation.141,159,160,161,162 In a recent study of transcriptional changes associated with AF, susceptibility to the arrhythmia was associated with decreased expression of targets of several transcription factors related to inflammation, oxidation, and cellular stress responses.163 However, it is unknown to what extent and at which time points such alterations influence the remodeling process that perpetuates AF. Moreover, rapid atrial rates activate fibroblasts to increase collagen-gene activity, and AF in isolation might promote cardiac fibrosis.131,133,134\nCardiac fibrosis is part of the maladaptive cardiac remodeling in response to cardiac injury164,165 and has been implicated in initiation and maintenance of AF.166 The mechanisms that are responsible for fibrosis and its consequences comprise many phenomena occurring at various scales, including molecular, organelle, cellular, and tissue scales.167 At the molecular scale are dynamics changes in the genome, the transcriptome, and the signaling pathways underlying the generation of profibrotic molecules168; cellular changes involve interactions among the various cardiac cells, including myocytes, fibroblasts or myofibroblasts, and inflammatory cells such as macrophages and neutrophils169; and tissue changes relate to the dynamics of scar, angiogenesis, electrical conduction, and contractility.153 Fibrosis can certainly act as an electrically insulating obstacle. Profibrotic stimuli promote differentiation of fibroblasts into activated myofibroblasts, which electronically couple to myocytes in vitro20,150,151,152; whether this occurs to a significant extent in AF atria in vivo remains uncertain. Fibrosis affects electrical propagation through slow, discontinuous conduction with “zigzag” propagation,170,171 reduced regional coupling,172 abrupt changes in fibrotic bundle size,173 interruption of bundle continuity, and micro-anatomical reentry.174\nAnother potentially important factor in AF-related atrial remodeling is fatty infiltration, which is known to increase in a number of myocardial pathophysiological conditions and is regarded as arrhythmogenic.175,176,177 Obesity is a known AF risk factor, and the increasing incidence of AF could be related to increasing rates of obesity.177,178 Obesity frequently coexists with other AF risk factors that improve in response to weight loss, emphasizing the importance of weight loss in AF risk factor management.179 Epicardial fatty infiltration occurs with obesity180 and has been associated with AF.177 Biofactors released from fat might promote fibrosis and myocardial 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