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Abstract：
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 R2 = 0.685, p<0.001), log (NOX4) (adjusted R2 = 0.622, p<0.001), log (NOX2) (adjusted R2 = 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.
摘要：
二维斑点追踪超声心动图（2DSTE）测量的左心房应变（LAS）被认为是LA结构重构的标志，但它仍然不确定。我们通过分析心血管手术患者的基因表达，研究了LAS检测心房重构包括纤维化的潜在用途和临床相关性。术前进行2DSTE131例（92例窦性心律[SR]患者包括阵发性房颤[PAF]，39房颤[AF]）接受心血管手术。心房样本取自左心耳,通过实时逆转录聚合酶链反应（RT-PCR）分析59例（24PAF，35AF).与左心房容积指数(LAVI)相关的左心房储集器应变(mLASr)平均值,左心房导管应变（mLAScd）。mLASr还与包括PAF在内的SR患者的左心房收缩应变（mLASct）相关。mLASr明显降低，LAVI更高，在AF组中，与SR患者相比，包括PAF。在AF患者中，编码I型胶原α1的COL1A1mRNA的表达显着增加（p=0.031）。mLASr与COL1A1表达水平呈负相关,多因素回归分析显示,mLASr是心房COL1A1表达水平的独立预测因子,即使在调整了年龄之后，性别,BMI。但是,mLAScd/mLASct和LAVI（bp）均与COL1A1基因表达无关。COL1A1mRNA的表达水平与ECM相关基因（COL3A1，FN1）密切相关。它还与ECM降解相关基因（MMP2，TIMP1和TIMP2），促纤维化细胞因子(TGFB1编码TGFβ1，END1，PDGFD，CTGF),氧化应激相关基因（NOX2，NOX4），ACE,炎症相关基因(NLRP，IL1B,MCP-1),和细胞凋亡(BAX)。在检查的纤维化相关基因中，单变量回归分析显示log(COL1A1)与log(TGFB1)相关(调整后R2=0.685,p<0.001),log(NOX4)(调整后的R2=0.622，p<0.001)，log(NOX2)(调整后的R2=0.611，p<0.001)，表明TGFB1和NOX4是COL1A1表达水平的有效独立决定因素。mLASr与ECM相关基因呈负相关，PAF患者的纤维化相关基因表达水平包括TGFB1，NOX2和NLRP3。低mLASr的PAF患者纤维化相关基因表达较高，与MLASr高的人相比。这些结果表明LASr与心房COL1A1基因表达相关，与纤维化相关基因表达相关。低LASr患者心房纤维化相关基因表达增加,即使是那些有PAF的人，强调LAS作为心血管手术患者LA纤维化标志物的实用性。
