Effect of doxycycline on chronic intermittent hypoxia-induced atrial remodeling in rats.

Abstract:

BACKGROUND:Atrial remodeling in the form of fibrosis is considered the basis in the development of atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on atrial remodeling induced by chronic intermittent hypoxia (CIH) and the mechanisms underlying such changes. METHODS:A total of 45 Sprague-Dawley rats were randomized into three groups: control group, CIH group, CIH with doxycycline treatment (CIH-D) group. A rat model of atrial remodeling was established by CIH and Masson staining was used to evaluate the extent of atrial fibrosis. We studied the expression levels of microRNA-1 (miR-1), microRNA-21 (miR-21), microRNA-29b (miR-29b), microRNA-30 (miR-30), microRNA-133a (miR-133a), microRNA-328 (miR-328), transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF). Atrial effective refractory period and AF inducibility were examined via isolated heart models of cardiac electrophysiology. RESULTS:Compared with the control rats, CIH rats showed higher atrial interstitial collagen deposition, increased AF inducibility, and increased miR-1, miR-21, miR-133a, miR-328, TGF-β1, and CTGF levels. Treatment with doxycycline significantly attenuated CIH-induced atrial fibrosis, improved AF inducibility, and reduced miR-1, miR-21, miR-133a, miR-328, TGF-β1, and CTGF. CONCLUSION:CIH induced significant atrial remodeling, which was attenuated by doxycycline in our rat model. These changes can be explained by the alterations initiated in the miR-133a/TGF-β1/CTGF pathway by doxycycline.

journal_name

Herz

journal_title

Herz

authors

Zhang K,Ma Z,Wang W,Liu R,Zhang Y,Yuan M,Li G

doi

10.1007/s00059-018-4768-1

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

668-675

issue

7

eissn

0340-9937

issn

1615-6692

pii

10.1007/s00059-018-4768-1

journal_volume

45

pub_type

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