Turkieh Annie, Weber Lukas, Chwastyniak Maggy, Baydar Simge, Beseme Olivia, Ernst Matthias, Ye Quianling, Amouyel Philippe, Podesser Bruno K, Kiss Attila, Pinet Florence
Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE, Université de Lille, Lille, France.
Ludwig Boltzmann Institute for Cardiovascular Research at the Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria.
J Cell Mol Med. 2024 Dec;28(23):e70290. doi: 10.1111/jcmm.70290.
Chronic pressure overload induces adverse cardiac remodelling characterised by left ventricular (LV) hypertrophy and fibrosis, leading to heart failure (HF). Identification of new biomarkers for adverse cardiac remodelling enables us to better understand this process and, consequently, to prevent HF. We recently identified clusterin (CLU) as a biomarker of cardiac remodelling and HF after myocardial infarction. The aim of this study was to investigate whether CLU expression is regulated in the heart and could be used as an indicator of adverse cardiac remodelling in response to pressure overload. We quantified CLU in the LV of mice subjected to transverse aortic constriction (TAC) and observed increased CLU mRNA levels and its mature protein form (m-CLU) compared to the sham. Interestingly, CLU mRNA levels were positively correlated with pro-hypertrophic (ANP, BNP, B-MHC), pro- and anti-fibrotic (TGFb, ColI and CILP) genes. In addition, m-CLU was positively correlated with LV hypertrophy, LV end diastolic and systolic diameters, and negatively correlated with LV ejection fraction. Finally, we observed that m-CLU levels only increased in TAC mice with severe cardiac remodelling and dysfunction without any significant difference in plasma CLU levels. This is the first study to demonstrate that cardiac expression of CLU is induced in the LV of TAC mice during adverse cardiac remodelling. However, plasma CLU levels could not be used as biomarkers of TAC-induced cardiac remodelling and dysfunction.
慢性压力超负荷会引发不良心脏重塑，其特征为左心室（LV）肥厚和纤维化，进而导致心力衰竭（HF）。识别不良心脏重塑的新生物标志物有助于我们更好地理解这一过程，从而预防HF。我们最近发现簇集蛋白（CLU）是心肌梗死后心脏重塑和HF的生物标志物。本研究的目的是调查CLU表达在心脏中是否受到调控，以及是否可作为压力超负荷时不良心脏重塑的指标。我们对接受主动脉缩窄（TAC）的小鼠左心室中的CLU进行了定量分析，发现与假手术组相比，TAC组小鼠的CLU mRNA水平及其成熟蛋白形式（m-CLU）均有所增加。有趣的是，CLU mRNA水平与促肥厚（ANP、BNP、β-MHC）、促纤维化和抗纤维化（TGFβ、ColI和CILP）基因呈正相关。此外，m-CLU与左心室肥厚、左心室舒张末期和收缩期直径呈正相关，与左心室射血分数呈负相关。最后，我们观察到m-CLU水平仅在具有严重心脏重塑和功能障碍的TAC小鼠中升高，而血浆CLU水平无显著差异。这是第一项证明在不良心脏重塑过程中TAC小鼠左心室中CLU的心脏表达被诱导的研究。然而，血浆CLU水平不能用作TAC诱导的心脏重塑和功能障碍的生物标志物。
