title: Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.
abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Fengping
authors.initials: F
authors.lastname: He
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Shuguo
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Liangqiu
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Shaochun
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Shebin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Zhanzhong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Jungang
authors.initials: J
authors.lastname: Pang
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department Institute of Cardiovascular Diseases, The Yuebei People's Hospital, Medical College, Shantou University, Shantou, Guangdong, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Weng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001281:Atrial Fibrillation / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D020746:Calcium Channels, L-Type / Q000097:blood* / Q000235:genetics; D004285:Dogs; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012214:Rheumatic Heart Disease / Q000097:blood / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020746:Calcium Channels, L-Type; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C079146:CACNA1C protein, human; C514350:CACNA1C protein, mouse; C525067:MIR223, human; C099252:oxidized low density lipoprotein