Establishment of a prediction model of changing trends in cardiac hypertrophy disease based on microarray data screening

Abstract

The aim of the present study was to construct a mathematical model to predict the changing trends of cardiac hypertrophy at gene level. Microarray data were downloaded from Gene Expression Omnibus database (accession, GSE21600), which included 35 samples harvested from the heart of Wistar rats on postoperative days 1 (D1 group), 6 (D6 group) and 42 (D42 group) following aorta ligation and sham operated Wistar rats, respectively. Each group contained six samples, with the exception of the samples harvested from the aorta ligated group after 6 days, where n=5. Differentially expressed genes (DEGs) were identified using a Limma package in R. Hierarchical clustering analysis was performed on common DEGs in order to construct a linear equation between the D1 and D42 groups, using linear discriminant analysis. Subsequent verification was performed using receiver operating characteristic (ROC) curve and the measurement data at day 42. A total of 319, 44 and 57 DEGs were detected in D1, D6 and D42 sample groups, respectively. AKIP1, ANKRD23, LTBP2, TGF-β2 and TNFRSF12A were identified as common DEGs in all groups. The predicted linear equation between D1 and D42 group was calculated to be y=1.526×-186.671. Assessment of the ROC curve demonstrated that the area under the curve was 0.831, with a specificity and sensitivity of 0.8. As compared with the predictive and measurement data at day 42, the consistency of the two sets of data was 76.5%. In conclusion, the present model may contribute to the early prediction of changing trends in cardiac hypertrophy disease at gene level.

Tnfrsf12a-Mediated Atherosclerosis Signaling and Inflammatory Response as a Common Protection Mechanism of Shuxuening Injection Against Both Myocardial and Cerebral Ischemia-Reperfusion Injuries

“…Among the DEGs in both, two overlapping genes are detected between the brain tissues (SXNI vs. CIRI) and myocardium (SXNI vs. MIRI) ( Figure 2 ), which are Calca (ENSMUSG00000030669) and Tnfrsf12a (ENSMUSG00000023905). Calca is associated with Parkinson diseases ( Buervenich et al, 2001 ) and essential hypertension ( Luo et al, 2008 ), while Tnfrsf12a is an important molecule in cardiac hypertrophy disease ( Ma et al, 2016 ), cardiac shock ( Wang W. et al, 2016 ) retinal inflammation ( Abcouwer et al, 2013 ), and atherosclerosis-related diseases ( Munoz-Garcia et al, 2006 , 2011 ; Moreno et al, 2013 ; Fernandez-Laso et al, 2017 ). Top 10 canonical pathways and top 6 functions were listed by the descending -log( p -value) score ( Figures 6C – F ).…”

Cardiomyocyte glucocorticoid and mineralocorticoid receptors directly and antagonistically regulate heart disease in mice

“…Compared to the single knockout hearts, Agt expression was reduced and Ccnd2, Hdac4, and Ankrd23 expression was increased in hearts lacking both receptors. Each of these gene changes has been reported to inhibit the hypertrophic response of cardiomyocytes (22,23,28,29). The cardioGRMRdKO hearts developed pathological cardiac hypertrophy as evidenced by the reactivation of the fetal cardiac gene program; however, LV hypertrophy was smaller in magnitude and slower to develop than observed in the cardioGRKO hearts.…”

“…Histone deacetylase 4 is a member of the class II histone deacetylases that suppress cardiac hypertrophy by inhibiting prohypertrophic transcription factors (27,28). Ankyrin repeat domain 23 is a member of the muscle ankyrin repeat protein family involved in muscle gene regulation and myofilament organization, and reduced expression of this gene has been associated with the development of cardiac hypertrophy (29). By limiting cardiac hypertrophy and promoting cardiomyocyte survival, the observed changes in these genes would protect the cardioGRMRdKO heart from disease.…”

Weighted gene co-expression network-based approach to identify key genes associated with anthracycline-induced cardiotoxicity and construction of miRNA-transcription factor-gene regulatory network

“…These findings along with our results suggest that the regulation of Ryr2 expression or activity may be a potential strategy for the treatment of AIC. Although the rest novel genes including Casq1, Fcgr2b, Postn, Tnfrsf12a, Ankrd23 and Scn3b have never been reported in AIC, several of them have been demonstrated associated with cardiomyopathy, myocardial ischemia–reperfusion injury, viral myocarditis, fibrosis, cardiac remodeling, arrhythmia and cardiac hypertrophy disease, respectively (Hasdemir et al 2010 ; Li et al 2009 ; Ma et al 2016 ; Yao et al 2020 ; Zhao et al 2018 ).…”