Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction, but no deficit in heart morphology

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.心脏重构指心肌损伤后心脏的形态、大小、结构与功能发生的改变。促炎性衔接蛋白髓系分化蛋白88（myeloid differentiation protein 88, MyD88）参与心脏重构进程。为探究MyD88过表达是否会在整体生物体水平上诱发自发性心脏重构，我们构建了携带心脏特异性启动子的转基因MyD88小鼠模型。该MyD88转基因小鼠（雄性，体重20~30 g，样本量n≈80）按照预期的孟德尔比例出生，其心脏与心肌细胞的形态与野生型对照小鼠无显著差异。尽管心脏重量未受影响，但与野生型对照相比，超声心动图检查结果显示MyD88转基因小鼠的心脏收缩功能轻度受损。此外，该心功能障碍表型与心房钠尿肽（Atrial Natriuretic Factor, ANF）及脑钠肽（Brain Natriuretic Peptide, BNP）的表达上调相关。综上，本研究数据为平衡的MyD88信号通路在维持成年心脏生理功能中的关键作用提供了新的证据。