Anti-NRG1 monoclonal antibody, clone l2H24

Hey2 gene mutations in both humans and mice have been associated with multiple cardiac defects. However, the currently reported localization of Hey2 in the ventricular compact zone cannot explain the wide variety of cardiac defects. Furthermore, it was reported that, in contrast to other organs, Notch doesn't regulate Hey2 in the heart. To determine the expression pattern and the regulation of Hey2, we used novel methods including RNAscope and a Hey2(CreERT2) knockin line to precisely determine the spatiotemporal expression pattern and level of Hey2 during cardiac development. We found that Hey2 is expressed in the endocardial cells of the atrioventricular canal and the outflow tract, as well as at the base of trabeculae, in addition to the reported expression in the ventricular compact myocardium. By disrupting several signaling pathways that regulate trabeculation and/or compaction, we found that, in contrast to previous reports, Notch signaling and Nrg1/ErbB2 regulate Hey2 expression level in myocardium and/or endocardium, but not its expression pattern: weak expression in trabecular myocardium and strong expression in compact myocardium. Instead, we found that FGF signaling regulates the expression pattern of Hey2 in the early myocardium, and regulates the expression level of Hey2 in a Notch1 dependent manner.

Aims: Myocardial infarction (MI) is accompanied with skeletal muscle abnormalities. The aims are to explore an optimal exercise mode to improve cardiac function and prevent skeletal muscle atrophy, and detect the possible mechanisms of exercise-induced inhibition of muscle atrophy. Main methods: Rats were subjected to four weeks of different types of exercise after MI surgery (resistance training, RT; moderated-intensity continuous aerobic exercise, MCE and high-intensity intermittent aerobic exercise, HIA). Cardiac function, histological changes of heart and skeletal muscle, oxidative stress, antioxidant capacity and the expression of muscle atrophy-related factors were detected in skeletal muscle. Key findings: The three types of exercise improved heart function, reduced cardiac fibrosis and increased muscle weight and cross-section area (CSA) of muscle fibers in different degrees. The survival rates of MI rats intervened by RT and MCE were higher than HIA. Exercise down-regulated the mRNA levels of murf1 and atrogin-1, decreased reactive oxygen species level, increased antioxidant capacity, regulated the expression of insulin-like growth factor 1 (IGF1), mechano growth factor (MGF), Neuregulin1 (NRG1) and Myostatin (MSTN), and activated Akt and Erk1/2 signalings in soleus muscle. Furthermore, CSA of muscle fibers and the expression of IGF1, MGF, NRG1 in skeletal muscle had correlations with cardiac function. Significance: RT and MCE are the first two choices for the early exercise rehabilitation following MI. All types of exercise can effectively inhibit skeletal muscle atrophy through increasing the antioxidant capacity, reducing oxidative stress and protein degradation, and regulating the growth factors expression in skeletal muscle.