Cardiac Hypertrophy Data Mining And Key Regulatory Molecular,NULP1,Functions Of Cardiac Remodeling

The occurrence and development of cardiac hypertrophy induced by pressure overload involves the synergistic effects of a series of transcriptional activators and inhibitors.The mechanism that their interaction triggers pathological gene transcription reprogramming is still unknown.We downloaded myocardial tissue microarray data of aortic stenosis-induced mouse myocardial hypertrophy from the NCBI GEO database.Clarified the main events in the development of myocardial hypertrophy and the order of occurrence.In the early stages of pressure overload,inflammation-related events in the myocardial tissue are the earliest changes in transcription levels.Sustained stress overload leads to a gradual increase in ribosome biosynthesis and protein synthesis related gene expression.After about 48 hours of pressure overload,transcriptional reprogramming related to cardiac remodeling is initiated,lasting until it peaked about 1 week later.In order to explore the key molecules that regulate myocardial remodeling during the period from 48 h to 1 week.The single cell data of the mouse model of cardiac hypertrophy were downloaded for analysis.Through weighted gene co-expression network analysis,it was found that 1 week after pressure overload,genes that are highly expressed in cardiomyocytes are mainly divided into three modules.The coexpressed genes in the blue module mainly participate in the process of myocardial remodeling.Therefore,through the enrichment analysis of upstream transcription factors of the genes in this module,we found the key candidate transcription factor,Srf,that regulates these genes.By collecting the reported regulatory molecules of Srf,it was found that Nulp1,a member of the base helix-loop-helix family,has the function of regulating the Srf gene,and some members of this protein family have been reported to be involved in the development of cardiac hypertrophy.Therefore,we believe that Nulp1 is a key candidate for regulating myocardial remodeling.In order to further verify the function of Nulp1 in the development of myocardial hypertrophy.We conducted Nulp1 knockout and overexpression experiments.The results showed that the knock-out of Nulp1 gene aggravated the pathological changes of myocardial hypertrophy caused by aortic stenosis,and the overexpression of Nulp1 significantly attenuated this pathological change.In short,based on data mining and functional verification of the mining results,Nulp1 has the function of inhibiting the development of myocardial hypertrophy.