Journal Article

Left atrial reservoir strain is a marker of atrial fibrotic remodeling in patients undergoing cardiovascular surgery: Analysis of gene expression

Takafumi Nakajima, Hirotsugu Fukuda, Akiko Haruyama, Shichiro Abe, Syotaro Obi, Ikuko Shibasaki, Takaaki Hasegawa, Shigeru Toyoda, Hiroko Yazawa, Shu Inami, Takuo Arikawa, Gaku Oguri, Taira Fukuda, Hirohisa Amano, Masashi Sakuma, Kentaro Minami, Yoshiyuki Kitagawa, Toshiaki Nakajima, Suguru Hirose

2024

Overview

Left atrial strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DSTE) is considered to be a marker of LA structural remodeling, but it remains unsettled. We investigated the potential usefulness and clinical relevance of LAS to detect atrial remodeling including fibrosis by analyzing gene expression in cardiovascular surgery patients. Preoperative 2DSTE was performed in 131 patients (92 patients with sinus rhythm [SR] patients including paroxysmal AF [PAF], 39 atrial fibrillation [AF]) undergoing cardiovascular surgery. Atrial samples were obtained from the left atrial appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases (24 PAF, 35 AF). Mean value of left atrial reservoir strain (mLASr) correlated with left atrial volume index (LAVI), and left atrial conduit strain (mLAScd). mLASr also correlated with left atrial contractile strain (mLASct) in SR patients including PAF. mLASr was significantly lower, and LAVI was higher, in the AF group, compared with SR patients including PAF. The expression of COL1A1 mRNA encoding collagen type I α1 significantly increased in AF patients (p = 0.031). mLASr negatively correlated with COL1A1 expression level, and multivariate regression analysis showed that mLASr was an independent predictor of atrial COL1A1 expression level, even after adjusting for age, sex, and BMI. But, neither mLAScd / mLASct nor LAVI (bp) correlated with COL1A1 gene expression. The expression level of COL1A1 mRNA strongly correlated with ECM-related genes (COL3A1, FN1). It also correlated ECM degradation-related genes (MMP2, TIMP1, and TIMP2), pro-fibrogenic cytokines (TGFB1 encoding TGFβ1, END1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ACE, inflammation-related genes (NLRP, IL1B, MCP-1), and apoptosis (BAX). Among the fibrosis-related genes examined, univariable regression analysis showed that log (COL1A1) was associated with log (TGFB1) (adjusted R 2 = 0.685, p<0.001), log (NOX4) (adjusted R 2 = 0.622, p<0.001), log (NOX2) (adjusted R 2 = 0.611, p<0.001), suggesting that TGFB1 and NOX4 was the potent independent determinants of COL1A1 expression level. mLASr negatively correlated with the ECM-related genes, and fibrosis-related gene expression level including TGFB1, NOX2, and NLRP3 in PAF patients. PAF patients with low mLASr had higher expression of the fibrosis-related gene expression, compared with those with high mLASr. These results suggest that LASr correlates with atrial COL1A1 gene expression associated with fibrosis-related gene expression. Patients with low LASr exhibit increased atrial fibrosis-related gene expression, even those with PAF, highlighting the utility of LAS as a marker for LA fibrosis in cardiovascular surgery patients.

• Publisher: Public Library of Science (PLoS),Public Library of Science
• Subject: Aged / Apoptosis / Appendages / Atrial fibrillation / Atrial Fibrillation - genetics / Atrial Fibrillation - metabolism / Atrial Fibrillation - pathology / Atrial Fibrillation - physiopathology / Atrial Fibrillation - surgery / Atrial Function, Left / Atrial Remodeling - genetics / BAX protein / Biology and Life Sciences / Biomarkers / Biomarkers - metabolism / Cardiac arrhythmia / Cardiovascular disease / Collagen / Collagen (type I) / Collagen Type I - genetics / Collagen Type I - metabolism / Collagen Type I, alpha 1 Chain / Connective tissue growth factor / Contractility / Correlation / CYBB protein / Echocardiography / Female / Fibronectins / Fibrosis / Gelatinase A / Gene expression / Genes / Growth factors / Heart Atria - metabolism / Heart Atria - pathology / Heart surgery / Humans / Kinases / Male / Medicine / Medicine and Health Sciences / Messenger RNA / Middle Aged / Monocyte chemoattractant protein 1 / NOX4 protein / Ostomy / Oxidants / Oxidizing agents / Patients / Physical Sciences / Platelet-derived growth factor / Polymerase chain reaction / Q / R / Real time / Regression analysis / Research and Analysis Methods / Research Article / Reverse transcription / RNA, Messenger - genetics / RNA, Messenger - metabolism / Science / Surgery / Tissue inhibitor of metalloproteinase 1 / Tissue inhibitor of metalloproteinase 2 / Transforming growth factor-b1 / Transforming growth factors