CIH treatment induced significant atrial fibrosis in our rat model, which was attenuated by doxycycline. These changes can be explained by alterations in the MMP and miR-21/ERK signaling pathways.

BackgroundAtrial remodeling especially in the form of fibrosis is the most important substrate of atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)-induced atrial remodeling and the pathophysiological mechanisms underlying such changes.Material/MethodsA total of 30 Sprague-Dawley rats were randomized into 3 groups: Control group, CIH group, and CIH with doxycycline treatment group. CIH rats were subjected to CIH 6 h/d for 30 days and treatment rats were administrated doxycycline while they received CIH. After the echocardiography examination, rats were sacrificed at 31 days. The tissues of atria were collected for histological and molecular biological experiments, Masson staining was used to evaluate the extent of atrial fibrosis, microRNA-21, and its downstream target phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K) were assessed.ResultsCompared to the control group, the CIH rats showed higher atrial interstitial collagen fraction, increased microRNA-21, PI3K levels, and decreased PTEN levels. Doxycycline treatment attenuated CIH-induced atrial fibrosis, reduced microRNA-21 and PI3K, and increased PTEN.ConclusionsCIH induced significant atrial remodeling, which was attenuated by doxycycline in our rat model. These changes may be explained due to alterations in the microRNA-21-related signaling pathways by doxycycline.

CIH-induced significant atrial remodeling in our rat model, which was attenuated by tolvaptan. These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-κB pathways by tolvaptan.

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