Moady Gassan, Ertracht Offir, Shuster-Biton Efrat, Daud Elias, Atar Shaul
The Cardiology Department, Galilee Medical Center, Nahariya 2210001, Israel.
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Biomedicines. 2023 Aug 22;11(9):2337. doi: 10.3390/biomedicines11092337.
Cardiac hypertrophy develops following different triggers of pressure or volume overload. In several previous studies, different hypertrophy types were demonstrated following alterations in extracellular signal-regulated kinase (ERK) pathway activation. In the current study, we studied two types of cardiac hypertrophy models in rats: eccentric and concentric hypertrophy. For the eccentric hypertrophy model, iron deficiency anemia caused by a low-iron diet was implemented, while surgical aortic constriction was used to induce aortic stenosis (AS) and concentric cardiac hypertrophy. The hearts were evaluated using echocardiography, histological sections, and scanning electron microscopy. The expression of ERK1/2 was analyzed using Western blot. During the study period, anemic rats developed eccentric hypertrophy characterized by an enlarged left ventricle (LV) cavity cross-sectional area (CSA) (59.9 ± 5.1 mm vs. 47 ± 8.1 mm, = 0.002), thinner septum (2.1 ± 0.3 mm vs. 2.5 ± 0.2 mm, < 0.05), and reduced left ventricular ejection fraction (LVEF) (52.6% + 4.7 vs. 60.3% + 2.8, < 0.05). Rats with AS developed concentric hypertrophy with a thicker septum (2.8 ± 0.6 vs. 2.4 ± 0.1 < 0.05), increased LV muscle cross-sectional area (79.5 ± 9.33 mm vs. 57.9 ± 5.0 mm, < 0.001), and increased LVEF (70.3% + 2.8 vs. 60.0% + 2.1, < 0.05). ERK1/2 expression decreased in the anemic rats and increased in the rats with AS. Nevertheless, the p-ERK and the p-MEK did not change significantly in all the examined models. We concluded that ERK1/2 expression was altered by the type of hypertrophy and the change in LVEF.
心脏肥大是在压力或容量超负荷等不同诱因作用下发展而来的。在先前的多项研究中，细胞外信号调节激酶（ERK）通路激活发生改变后出现了不同类型的肥大。在本研究中，我们在大鼠中研究了两种心脏肥大模型：离心性肥大和向心性肥大。对于离心性肥大模型，采用低铁饮食导致缺铁性贫血来构建，而通过手术性主动脉缩窄来诱导主动脉狭窄（AS）和向心性心脏肥大。使用超声心动图、组织切片和扫描电子显微镜对心脏进行评估。采用蛋白质免疫印迹法分析ERK1/2的表达。在研究期间，贫血大鼠出现了离心性肥大，其特征为左心室（LV）腔横截面积（CSA）增大（59.9±5.1平方毫米对47±8.1平方毫米，P = 0.002）、室间隔变薄（2.1±0.3毫米对2.5±0.2毫米，P<0.05）以及左心室射血分数（LVEF）降低（52.6% + 4.7对60.3% + 2.8，P<0.05）。患有AS的大鼠出现了向心性肥大，室间隔增厚（2.8±0.6对2.4±0.1，P<0.05）、左心室肌肉横截面积增加（79.5±9.33平方毫米对57.9±5.0平方毫米，P<0.001）以及LVEF增加（70.3% + 2.8对60.0% + 2.1，P<0.05）。ERK1/2表达在贫血大鼠中降低，而在患有AS的大鼠中增加。然而，在所有检测模型中，磷酸化ERK（p-ERK）和磷酸化丝裂原活化蛋白激酶激酶（p-MEK）没有显著变化。我们得出结论，ERK1/2表达因肥大类型和LVEF的变化而改变。
