Abstract：
:Atrial fibrillation (AF) is associated with oxidative stress and Ca2+-handling abnormalities in atrial myocytes. Our prior study has demonstrated the involvement of CD44, a membrane receptor for hyaluronan (HA), in the pathogenesis of AF. This study further evaluated whether CD44 and its related signaling mediate atrial tachycardia-induced oxidative stress and Ca2+-handling abnormalities. Tachypacing in atrium-derived myocytes (HL-1 cell line) induced the activation of CD44-related signaling, including HA and HA synthase (HAS) expression. Blocking HAS/HA/CD44 signaling attenuated tachypacing-induced oxidative stress (NADPH oxidase [NOX] 2/4 expression) and Ca2+-handling abnormalities (oxidized Ca2+/calmodulin-dependent protein kinase II [ox-CaMKII] and phospho-ryanodine receptor type 2 [p-RyR2] expression) in HL-1 myocytes. Furthermore, a direct association between CD44 and NOX4 was documented in tachy-paced HL-1 myocytes and atrial tissues from AF patients. In vitro, Ca2+ spark frequencies in atrial myocytes isolated from CD44-/- mice were lower than those from wild-type mice. Furthermore, administration of an anti-CD44 blocking antibody in atrial myocytes isolated from wild-type mice diminished the frequency of Ca2+ spark. Ex vivo tachypacing models of CD44-/- mice exhibited a lower degree of oxidative stress and expression of ox-CaMKII/p-RyR2 in their atria than those of wild-type mice. In vivo, burst atrial pacing stimulated a less inducibility of AF in CD44-/-mice than in wild-type mice. In conclusion, atrial tachypacing-induced Ca2+-handling abnormalities are mediated via CD44/NOX4 signaling, which provides a possible explanation for the development of AF.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Chen WJ,Chang SH,Chan YH,Lee JL,Lai YJ,Chang GJ,Tsai FC,Yeh YHdoi
10.1016/j.yjmcc.2019.08.006subject
Has Abstractpub_date
2019-10-01 00:00:00pages
67-78eissn
0022-2828issn
1095-8584pii
S0022-2828(19)30167-1journal_volume
135pub_type
杂志文章abstract：:Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiova...
journal_title：Journal of molecular and cellular cardiology
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pub_type： 杂志文章,评审
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
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journal_title：Journal of molecular and cellular cardiology
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