Increased neprilysin expression is linked to atrial fibrotic remodeling in cardiovascular surgery patients

IF 2.5 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

IJC Heart and Vasculature Pub Date : 2025-03-17 DOI:10.1016/j.ijcha.2025.101647

Toshiaki Nakajima , Akiko Haruyama , Taira Fukuda , Kentaro Minami , Takafumi Nakajima , Takaaki Hasegawa , Seiko Tokoi , Syotaro Obi , Gaku Oguri , Masashi Sakuma , Ikuko Shibasaki , Hirotsugu Fukuda , Shigeru Toyoda

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引用次数: 0

Abstract

Background

Neprilysin (NEP) is a membrane-bound neutral endopeptidase with various physiological functions. We investigated the roles of NEP in atrial fibrotic remodeling and atrial fibrillation (AF) in patients undergoing cardiovascular surgery.

Methods

Atrial tissue samples were obtained from left atrium (LA) appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction in 61 cases (25 paroxysmal fibrillation (PAF), 36 AF). Adipose tissue (AT) mRNA expression levels were also analyzed. Western blotting and immunohistochemical staining were used for determining tissue protein expression. Serum NEP levels were measured by enzyme-linked immunosorbent assay (ELISA). Two-dimensional speckle tracking echocardiography was performed to measure mean left atrial reservoir strain (mLASr) to evaluate atrial remodeling in pre-operative patients and control participants.

Results

Immunohistochemical staining and western blotting revealed NEP expression in both AT and LA. Serum NEP levels did not correlate with NEP mRNA or protein expression in AT and LA. NEP mRNA expression levels correlated with fibrosis-related gene expression. NEP mRNA, protein, and fibrosis-related gene expression levels increased in PAF patients with low mLASr compared with high mLASr. PAF patients with high NEP mRNA expression showed increased fibrosis-related gene expression compared with those with low NEP expression. Multiple regression analysis revealed that NEP mRNA expression level was an independent variable for predicting fibrosis-related gene expression, whereas NOX4 and NLRP3 were independent variables for predicting NEP expression levels.

Conclusions

Increased atrial expression of NEP is linked to atrial fibrotic remodeling, and the development of AF in patients undergoing cardiovascular surgery.

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来源期刊

IJC Heart and Vasculature Medicine-Cardiology and Cardiovascular Medicine

CiteScore

4.90

自引率

10.30%

发文量

216

审稿时长

56 days

期刊介绍： IJC Heart & Vasculature is an online-only, open-access journal dedicated to publishing original articles and reviews (also Editorials and Letters to the Editor) which report on structural and functional cardiovascular pathology, with an emphasis on imaging and disease pathophysiology. Articles must be authentic, educational, clinically relevant, and original in their content and scientific approach. IJC Heart & Vasculature requires the highest standards of scientific integrity in order to promote reliable, reproducible and verifiable research findings. All authors are advised to consult the Principles of Ethical Publishing in the International Journal of Cardiology before submitting a manuscript. Submission of a manuscript to this journal gives the publisher the right to publish that paper if it is accepted. Manuscripts may be edited to improve clarity and expression.