PDF(Pubmed)
Abstract：
BACKGROUND: Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics.
RESULTS: The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II.
CONCLUSIONS: The study demonstrates ANP\'s potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP\'s effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.
RESULTS: The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II.
CONCLUSIONS: The study demonstrates ANP\'s potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP\'s effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.
摘要：
背景：心房颤动（AF），一种普遍的心律失常，与心房纤维化密切相关，一个主要的病理因素。心房纤维化发展的核心是心肌炎症。本研究的重点是心房利钠肽（ANP）及其在减轻心房纤维化中的作用，旨在阐明ANP发挥其作用的具体机制，强调成纤维细胞动力学。
结果：该研究涉及40只Sprague-Dawley大鼠，分为四组：对照组，血管紧张素II（AngII），AngII+ANP,只有ANP。AngII和AngII+ANP组给予1µg/kg/minAngII，AngII+ANP和ANP组均接受0.1µg/kg/min的ANP，持续14天。心脏成纤维细胞用于体外验证所提出的机制。研究观察到AngⅡ和AngⅡ+ANP组大鼠血压升高,体重下降,在AngII组中更明显。舒张功能障碍,AngII组的一个特征，由ANP缓解。此外,ANP显著降低AngII诱导的心房纤维化，肌成纤维细胞增殖，胶原蛋白过度表达，巨噬细胞浸润，白细胞介素6（IL-6）和生腱蛋白C（TN-C）的表达升高。转录组测序表明AngII组中PI3K/Akt信号增强。此外，体外研究表明，ANP，与PI3K抑制剂LY294002一起,有效降低PI3K/Akt通路的激活和TN-C的表达,胶原蛋白-I，和胶原蛋白III，由AngII诱导。
结论：研究表明ANP在抑制心肌炎症和减少心房纤维化方面具有潜力。值得注意的是,ANP对抗心房纤维化的作用似乎是通过抑制AngII诱导的PI3K/Akt-Tenascin-C信号通路介导的。这些见解增强了我们对AF发病机制的理解，并将ANP定位为治疗心房纤维化的潜在治疗剂。
结果：该研究涉及40只Sprague-Dawley大鼠，分为四组：对照组，血管紧张素II（AngII），AngII+ANP,只有ANP。AngII和AngII+ANP组给予1µg/kg/minAngII，AngII+ANP和ANP组均接受0.1µg/kg/min的ANP，持续14天。心脏成纤维细胞用于体外验证所提出的机制。研究观察到AngⅡ和AngⅡ+ANP组大鼠血压升高,体重下降,在AngII组中更明显。舒张功能障碍,AngII组的一个特征，由ANP缓解。此外,ANP显著降低AngII诱导的心房纤维化，肌成纤维细胞增殖，胶原蛋白过度表达，巨噬细胞浸润，白细胞介素6（IL-6）和生腱蛋白C（TN-C）的表达升高。转录组测序表明AngII组中PI3K/Akt信号增强。此外，体外研究表明，ANP，与PI3K抑制剂LY294002一起,有效降低PI3K/Akt通路的激活和TN-C的表达,胶原蛋白-I，和胶原蛋白III，由AngII诱导。
结论：研究表明ANP在抑制心肌炎症和减少心房纤维化方面具有潜力。值得注意的是,ANP对抗心房纤维化的作用似乎是通过抑制AngII诱导的PI3K/Akt-Tenascin-C信号通路介导的。这些见解增强了我们对AF发病机制的理解，并将ANP定位为治疗心房纤维化的潜在治疗剂。
