Cardiovascular diseases (CVDs) represent a major concern for global health, whose mechanistic understanding is complicated by a complex interplay between genetic predisposition and environmental factors. Specifically, heart failure (HF), encompassing dilated cardiomyopathy (DC), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM), is a topic of substantial interest in basic and clinical research. Here, we used a Partial Correlation Coefficient-based algorithm (PCC) within the context of a meta-analysis framework to construct a Gene Regulatory Network (GRN) that identifies key regulators whose activity is perturbed in Heart Failure. By integrating data from multiple independent studies, our approach unveiled crucial regulatory associations between transcription factors (TFs) and structural genes, emphasizing their pivotal roles in regulating metabolic pathways, such as fatty acid metabolism, oxidative stress response, epithelial-to-mesenchymal transition, and coagulation. In addition to known associations, our analysis also identified novel regulators, including the identification of TFs FPM315 and OVOL2, which are implicated in dilated cardiomyopathies, and TEAD1 and TEAD2 in both dilated and ischemic cardiomyopathies. Moreover, we uncovered alterations in adipogenesis and oxidative phosphorylation pathways in hypertrophic cardiomyopathy and discovered a role for IL2 STAT5 signaling in heart failure. Our findings underscore the importance of TF activity in the initiation and progression of cardiac disease, highlighting their potential as pharmacological targets.

Pepe, G., Appierdo, R., Ausiello, G., Helmer-Citterich, M., Gherardini, P.f. (2024). A Meta-Analysis Approach to Gene Regulatory Network Inference Identifies Key Regulators of Cardiovascular Diseases. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25(8) [10.3390/ijms25084224].

A Meta-Analysis Approach to Gene Regulatory Network Inference Identifies Key Regulators of Cardiovascular Diseases

Pepe, Gerardo;Appierdo, Romina;Ausiello, Gabriele;Helmer-Citterich, Manuela
;
Gherardini, Pier Federico
2024-04-11

Abstract

Cardiovascular diseases (CVDs) represent a major concern for global health, whose mechanistic understanding is complicated by a complex interplay between genetic predisposition and environmental factors. Specifically, heart failure (HF), encompassing dilated cardiomyopathy (DC), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM), is a topic of substantial interest in basic and clinical research. Here, we used a Partial Correlation Coefficient-based algorithm (PCC) within the context of a meta-analysis framework to construct a Gene Regulatory Network (GRN) that identifies key regulators whose activity is perturbed in Heart Failure. By integrating data from multiple independent studies, our approach unveiled crucial regulatory associations between transcription factors (TFs) and structural genes, emphasizing their pivotal roles in regulating metabolic pathways, such as fatty acid metabolism, oxidative stress response, epithelial-to-mesenchymal transition, and coagulation. In addition to known associations, our analysis also identified novel regulators, including the identification of TFs FPM315 and OVOL2, which are implicated in dilated cardiomyopathies, and TEAD1 and TEAD2 in both dilated and ischemic cardiomyopathies. Moreover, we uncovered alterations in adipogenesis and oxidative phosphorylation pathways in hypertrophic cardiomyopathy and discovered a role for IL2 STAT5 signaling in heart failure. Our findings underscore the importance of TF activity in the initiation and progression of cardiac disease, highlighting their potential as pharmacological targets.
11-apr-2024
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11
English
Con Impact Factor ISI
cardiomyopathy
cardiovascular disease
gene regulatory network
Pepe, G., Appierdo, R., Ausiello, G., Helmer-Citterich, M., Gherardini, P.f. (2024). A Meta-Analysis Approach to Gene Regulatory Network Inference Identifies Key Regulators of Cardiovascular Diseases. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25(8) [10.3390/ijms25084224].
Pepe, G; Appierdo, R; Ausiello, G; Helmer-Citterich, M; Gherardini, Pf
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/361483
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