Notch1 Is Involved in Physiologic Cardiac Hypertrophy of Mice via the p38 Signaling Pathway after Voluntary Running

Abstract

Appropriate exercise such as voluntary wheel-running can induce physiological cardiac hypertrophy. Notch1 plays an important role in cardiac hypertrophy; however, the experimental results are inconsistent. In this experiment, we aimed to explore the role of Notch1 in physiological cardiac hypertrophy. Twenty-nine adult male mice were randomly divided into a Notch1 heterozygous deficient control (Notch1+/− CON) group, a Notch1 heterozygous deficient running (Notch1+/− RUN) group, a wild type control (WT CON) group, and a wild type running (WT RUN) group. Mice in the Notch1+/− RUN and WT RUN groups had access to voluntary wheel-running for two weeks. Next, the cardiac function of all of the mice was examined by echocardiography. The H&E staining, Masson trichrome staining, and a Western blot assay were carried out to analyze cardiac hypertrophy, cardiac fibrosis, and the expression of proteins relating to cardiac hypertrophy. After two-weeks of running, the Notch1 receptor expression was decreased in the hearts of the WT RUN group. The degree of cardiac hypertrophy in the Notch1+/− RUN mice was lower than that of their littermate control. Compared to the Notch1+/− CON group, Notch1 heterozygous deficiency could lead to a decrease in Beclin-1 expression and the ratio of LC3II/LC3I in the Notch1+/− RUN group. The results suggest that Notch1 heterozygous deficiency could partly dampen the induction of autophagy. Moreover, Notch1 deficiency may lead to the inactivation of p38 and the reduction of β-catenin expression in the Notch1+/− RUN group. In conclusion, Notch1 plays a critical role in physiologic cardiac hypertrophy through the p38 signaling pathway. Our results will help to understand the underlying mechanism of Notch1 on physiological cardiac hypertrophy.

Effects of time-restricted exercise on activity rhythms and exercise-induced adaptations in the heart

“…It is also possible that a dose-dependent increase in cardiac hypertrophy was seen, where the larger volume of training done by EAP mice elicited greater hypertrophy. While this is possible, other studies have shown significant cardiac hypertrophy in a period of 2 weeks 37 . During the weeks 5 and 6 of our study, here was not a significantly different distance ran by EAP and LAP mice, suggesting that an equal exercise stimulus occurred for the final 2 weeks.…”

scKEPLM: Knowledge enhanced large-scale pre-trained language model for single-cell transcriptomics

“…6d and Supplementary Table S3), identifying five related pathways. Of these, pathways 1 and 3 are related to the Notch1 gene, further highlighting Notch1's essential role in embryonic development and heart formation and its role as a crucial factor in the proliferation and differentiation of cardiac stem cells [31]. Inhibition of Notch1 signaling could lead to life-threatening dilated cardiomyopathy, emphasizing that scKEPLM can not only validate known disease-related genes and pathways but also expand our perspectives in researching cardiac disease biomarkers and therapeutic targets.…”