左心室和右心室肥厚模型研究PAPP-A介导的IGFBP-4切割——一种调节成年大鼠IGF生物利用度的机制
Left Ventricular and Right Ventricular Hypertrophy Modelling to Study PAPP-A-Mediated IGFBP-4 Cleavage-a Mechanism That Regulates IGF Bioavailability in Adult Rats.
摘要(中文译文)
病理性心肌肥厚是心力衰竭的主要诱因，其特征为心房和心室体积的异常增大。在心室肥厚的背景下，右心室（RV）对肥厚的抵抗能力弱于左心室（LV）。胰岛素样生长因子（IGF-1和IGF-2）对细胞生长至关重要，并具有心脏保护作用。妊娠相关血浆蛋白-A（PAPP-A）是一种蛋白酶，可切割胰岛素样生长因子结合蛋白-4（IGFBP-4），从而增强IGF的生物利用度。本研究探讨了PAPP-A介导的IGFBP-4蛋白水解——这可能是右心室肥厚（RVH）和左心室肥厚（LVH）大鼠模型中IGF释放调节的一种机制。RVH通过野百合碱诱导，LVH通过肾血管性高血压（1肾1夹（1K1C）模型）诱导。采用尾套体积描记法测量收缩压。通过心脏形态计量学评估心腔质量。通过肌钙蛋白I免疫细胞化学确认心肌细胞纯度。采用荧光免疫分析法测定血浆B型利钠肽（BNP）和C端IGFBP-4（CT-IGFBP-4）浓度。RVH和LVH模型成功建立，RV质量增加1.6倍（< 0.0001），LV质量增加1.3倍（< 0.05）。LVH大鼠血浆BNP较对照组高2-3倍。肥厚的心肌细胞分泌的BNP显著多于对照组，LVH和RVH分别增加3.3倍和4.1倍。PAPP-A介导的IGFBP-4蛋白水解在RVH中较对照组高4倍，但在LVH中未受影响。这些发现表明，PAPP-A特异性增强的IGFBP-4蛋白水解主要发生于RVH，提示两个心室中IGF生物利用度存在差异，并凸显PAPP-A作为增强RVH抗肥厚能力的潜在靶点。
Abstract
Pathological cardiac hypertrophy, a major contributor to heart failure, is characterized by an abnormal increase in the size of atria and ventricles. In the context of ventricular hypertrophy, the right ventricle (RV) exhibits less resistance to hypertrophy than the left one (LV). Insulin-like growth factors (IGF-1 and IGF-2) are critical for cell growth and provide cardioprotective effects. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that cleaves insulin-like growth factor-binding protein-4 (IGFBP-4) and enhances IGF bioavailability. This study investigated PAPP-A-mediated IGFBP-4 proteolysis-one possible mechanism of IGF release regulation in rat models of right ventricular (RVH) and left ventricular (LVH) hypertrophy. RVH was induced with monocrotaline, and LVH via renovascular hypertension (1 Kidney 1 Clip (1K1C) model). Systolic blood pressure was measured using tail-cuff plethysmography. Heart morphometry was used to assess the mass of cardiac chambers. Cardiomyocyte purity was confirmed via troponin I immunocytochemistry. Plasma natriuretic type-B peptide (BNP) and C-terminal IGFBP-4 (CT-IGFBP-4) concentrations were quantified by fluoroimmunoassay. RVH and LVH were successfully modelled, with 1.6-fold and 1.3-fold increases in RV ( < 0.0001) and LV masses ( < 0.05), respectively. Plasma BNP was 2-3 times higher in LVH versus control rats. Hypertrophied cardiomyocytes secreted significantly more BNP than controls, showing 3.3-fold and 4.1-fold increases in LVH and RVH, respectively. PAPP-A-mediated IGFBP-4 proteolysis was 4-fold higher in RVH compared to control, but unaffected in LVH. These findings suggest that PAPP-A-specific elevation of IGFBP-4 proteolysis occurs predominantly in RVH, suggesting a differential IGF bioavailability in both ventricles and highlighting PAPP-A as a potential target to increase RVH resistance to hypertrophy.
如何引用
AMA
Marina M Artemieva, Arina V Makeeva, Daria A Adasheva, Viacheslav E Shein, Alexey G Katrukha, Alexander B Postnikov, et al. Left Ventricular and Right Ventricular Hypertrophy Modelling to Study PAPP-A-Mediated IGFBP-4 Cleavage-a Mechanism That Regulates IGF Bioavailability in Adult Rats.. International journal of molecular sciences. 2026; doi:10.3390/ijms27062761.
APA
Marina M Artemieva, Arina V Makeeva, Daria A Adasheva, Viacheslav E Shein, Alexey G Katrukha, Alexander B Postnikov, et al (2026). Left Ventricular and Right Ventricular Hypertrophy Modelling to Study PAPP-A-Mediated IGFBP-4 Cleavage-a Mechanism That Regulates IGF Bioavailability in Adult Rats.. International journal of molecular sciences. https://doi.org/10.3390/ijms27062761
GB/T 7714
Marina M Artemieva, Arina V Makeeva, Daria A Adasheva, Viacheslav E Shein, Alexey G Katrukha, Alexander B Postnikov, et al. Left Ventricular and Right Ventricular Hypertrophy Modelling to Study PAPP-A-Mediated IGFBP-4 Cleavage-a Mechanism That Regulates IGF Bioavailability in Adult Rats.[J]. International journal of molecular sciences, 2026 doi:10.3390/ijms27062761.
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