Department of Nutrition and Food Hygiene, School of Public Health, Dalian Medical University, Dalian 116004, China.
Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116000, China.
Biomed Pharmacother. 2019 Jun;114:108804. doi: 10.1016/j.biopha.2019.108804. Epub 2019 Mar 22.
B lymphocytes have been shown to contribute to autoimmune diseases via producing antibodies and proinflammatory cytokines. Depletion of B cells by blocking CD20 can inhibit these diseases. Here we examined whether an antibody against CD20, rituximab (RTX) (Rituxan), used clinically in oncology could have similar anti-inflammatory effects in cardiac remodeling and heart failure (HF) in mice. Cardiac remodeling was established by pressure overload induced by transverse aortic constriction (TAC). Wild-type (WT) male C57BL/6 J mice were subjected to pressure overload by using transverse aortic constriction and then received RTX for 4 weeks. Administration of RTX markedly improves in vivo heart function, and suppressed heart chamber dilation, myocyte hypertrophy, fibrosis and oxidative stress in mice after TAC operation. RTX treatment also reversed established hypertrophic remodeling induced by TAC. Moreover, TAC-induced activation of multiple signaling pathways including calcineurin A, ERK1/2, STAT3, TGFβ/Smad2/3 and IKKα/β/NF-kB were remarkably attenuated in RTX-treated hearts compared with controls. These inhibitory effects of RTX were associated with inhibition of proinflammatory cytokine expression and Th2 cytokine-mediated IgG production from B cells. In conclusion, this study identifies that administration of RTX can inhibit pressure overload-induced cardiac remodeling and dysfunction in mice, and suggest that RTX may be a promising drug for treating hypertrophic disease.
B 淋巴细胞通过产生抗体和促炎细胞因子而被证明在自身免疫性疾病中发挥作用。通过阻断 CD20 来耗尽 B 细胞可以抑制这些疾病。在这里，我们研究了一种针对 CD20 的抗体，利妥昔单抗（RTX）（Rituxan），在肿瘤学中临床应用是否对小鼠心脏重构和心力衰竭（HF）具有类似的抗炎作用。心脏重构通过横主动脉缩窄（TAC）引起的压力超负荷来建立。野生型（WT）雄性 C57BL/6J 小鼠通过横主动脉缩窄进行压力超负荷，然后接受 RTX 治疗 4 周。RTX 给药可显著改善体内心脏功能，并抑制 TAC 手术后小鼠的心室扩张、心肌细胞肥大、纤维化和氧化应激。RTX 治疗还可逆转 TAC 诱导的已建立的肥大重构。此外，与对照组相比，RTX 治疗的心脏明显减弱了 TAC 诱导的多种信号通路的激活，包括钙调神经磷酸酶 A、ERK1/2、STAT3、TGFβ/Smad2/3 和 IKKα/β/NF-kB。RTX 的这些抑制作用与抑制促炎细胞因子表达和 B 细胞产生 Th2 细胞因子介导的 IgG 有关。总之，本研究表明，RTX 的给药可以抑制小鼠压力超负荷诱导的心脏重构和功能障碍，并表明 RTX 可能是治疗肥大性疾病的有前途的药物。
