Zhang Zhi-Dong, Lian Ting, Cheng Quan-Yi, Zhu Mei-Ping, Lv Jian-Feng
Department of Cardiovasology, First Affiliated Hospital of Qiqihar Medical College, Qiqihar Medical University, Qiqihar, 161000, China.
Department of Physiology, College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
Curr Med Sci. 2024 Dec;44(6):1071-1080. doi: 10.1007/s11596-024-2952-5. Epub 2024 Dec 14.
To investigate whether cardiac mast cells (MCs) participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4 (TRPV4).
Pressure overload-induced myocardial hypertrophy was induced via abdominal aortic constriction (AAC). Myocardial hypertrophy was evaluated by measuring the heart weight index (HW/BW), lung weight index (LW/BW), ratio of heart weight to tibia length (HW/TL), ratio of lung weight to tibia length (LW/TL), and cross-sectional area of myocardial cells. qRT-PCR was used to detect the mRNA expression of TRPV4. Western blotting was used to detect the protein expression of TRPV4, mast cell tryptase, myosin heavy chain beta (β-MHC), calcineurin A (CnA), and nuclear factor of activated T-cell c3 (NFATc3). ELISA was used to measure the levels of brain natriuretic peptide (BNP) and histamine. Fluo4 AM was used to detect the calcium signal in H9c2 myocardial cells.
Compared with those of the sham rats, the myocardial mast cells, tryptase, HW/BW, LW/BW, HW/TL, and LW/TL, the cross-sectional area of the myocardial cells, and the expression of β-MHC, TRPV4, CnA, and NFATc3 in the myocardial tissue and the serum BNP of the AAC-treated rats increased significantly, whereas the MC stabilizer cromolyn sodium (CS) reversed these indicators. In H9c2 cardiomyocytes, treatment with histamine and the TRPV4 agonist GSK1016790A upregulated the expression of TRPV4, β-MHC, BNP, CnA and NFATc3 and increased calcium ion influx, whereas these effects were inhibited by the H2 receptor inhibitor famotidine and the TRPV4 inhibitor HC067047.
Cardiac MCs participate in pressure overload-induced myocardial hypertrophy through the upregulation of TRPV4 via its mediator histamine, and the Ca/CnA/NFATc3 signaling pathway is involved in this process.
研究心脏肥大细胞（MCs）是否通过调节瞬时受体电位香草酸受体4（TRPV4）参与压力超负荷诱导的心肌肥大。
通过腹主动脉缩窄（AAC）诱导压力超负荷诱导的心肌肥大。通过测量心脏重量指数（HW/BW）、肺重量指数（LW/BW）、心脏重量与胫骨长度之比（HW/TL）、肺重量与胫骨长度之比（LW/TL）以及心肌细胞横截面积来评估心肌肥大。采用qRT-PCR检测TRPV4的mRNA表达。采用蛋白质免疫印迹法检测TRPV4、肥大细胞类胰蛋白酶、肌球蛋白重链β（β-MHC）、钙调神经磷酸酶A（CnA）和活化T细胞核因子c3（NFATc3）的蛋白表达。采用酶联免疫吸附测定法（ELISA）测量脑钠肽（BNP）和组胺水平。采用Fluo4 AM检测H9c2心肌细胞中的钙信号。
与假手术组大鼠相比，AAC处理组大鼠心肌肥大细胞、类胰蛋白酶、HW/BW、LW/BW、HW/TL和LW/TL、心肌细胞横截面积以及心肌组织中β-MHC、TRPV4、CnA和NFATc3的表达及血清BNP显著增加，而MC稳定剂色甘酸钠（CS）可逆转这些指标。在H9c2心肌细胞中，组胺和TRPV4激动剂GSK1016790A处理上调了TRPV4、β-MHC、BNP、CnA和NFATc3的表达并增加了钙离子内流，而这些作用被H2受体抑制剂法莫替丁和TRPV4抑制剂HC067047抑制。
心脏MCs通过其介质组胺上调TRPV4参与压力超负荷诱导的心肌肥大，且Ca/CnA/NFATc3信号通路参与此过程。
