Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias

Crespo-García, T.; Cámara-Checa, A.; Dago, M.; Rubio-Alarcón, M.; Rapún, J.; Tamargo, J.; Delpón, E.; Caballero, R.

doi:10.1016/j.bcp.2022.115206

Cited by 5 publications

(6 citation statements)

References 237 publications

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“…Ion channels, specifically sodium and potassium channels, are encoded by five of these genes. As a result, two of these genes, KCNN2 and KCNJ5, have developed an association with the action potential of the atria [ 43 ]. KCNN2 encodes the channel SK2, a calcium-dependent potassium channel [ 43 ].…”

Section: Multi-omics Approaches Investigating Genes Associated With A...mentioning

confidence: 99%

“…As a result, two of these genes, KCNN2 and KCNJ5, have developed an association with the action potential of the atria [ 43 ]. KCNN2 encodes the channel SK2, a calcium-dependent potassium channel [ 43 ]. This creates a heteromeric channel complex with the SK3 protein produced by a gene reported to be associated with AF in a previous GWAS study, the KCNN3 gene [ 38 , 40 ].…”

Section: Multi-omics Approaches Investigating Genes Associated With A...mentioning

confidence: 99%

“…This creates a heteromeric channel complex with the SK3 protein produced by a gene reported to be associated with AF in a previous GWAS study, the KCNN3 gene [ 38 , 40 ]. The KCNJ5 gene helps form the IKACh channel complex by encoding Kir3.4, a potassium channel [ 43 ]. This produces heteromers with Kir3.1.…”

Section: Multi-omics Approaches Investigating Genes Associated With A...mentioning

confidence: 99%

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Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility

et al. 2023

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Atrial fibrillation (AF) and heart failure (HF) contribute to about 45% of all cardiovascular disease (CVD) deaths in the USA and around the globe. Due to the complex nature, progression, inherent genetic makeup, and heterogeneity of CVDs, personalized treatments are believed to be critical. To improve the deciphering of CVD mechanisms, we need to deeply investigate well-known and identify novel genes that are responsible for CVD development. With the advancements in sequencing technologies, genomic data have been generated at an unprecedented pace to foster translational research. Correct application of bioinformatics using genomic data holds the potential to reveal the genetic underpinnings of various health conditions. It can help in the identification of causal variants for AF, HF, and other CVDs by moving beyond the one-gene one-disease model through the integration of common and rare variant association, the expressed genome, and characterization of comorbidities and phenotypic traits derived from the clinical information. In this study, we examined and discussed variable genomic approaches investigating genes associated with AF, HF, and other CVDs. We collected, reviewed, and compared high-quality scientific literature published between 2009 and 2022 and accessible through PubMed/NCBI. While selecting relevant literature, we mainly focused on identifying genomic approaches involving the integration of genomic data; analysis of common and rare genetic variants; metadata and phenotypic details; and multi-ethnic studies including individuals from ethnic minorities, and European, Asian, and American ancestries. We found 190 genes associated with AF and 26 genes linked to HF. Seven genes had implications in both AF and HF, which are SYNPO2L, TTN, MTSS1, SCN5A, PITX2, KLHL3, and AGAP5. We listed our conclusion, which include detailed information about genes and SNPs associated with AF and HF.

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Section: Multi-omics Approaches Investigating Genes Associated With A...mentioning

confidence: 99%

Section: Multi-omics Approaches Investigating Genes Associated With A...mentioning

confidence: 99%

Section: Multi-omics Approaches Investigating Genes Associated With A...mentioning

confidence: 99%

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Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility

et al. 2023

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“…Generally speaking, transcription factors bind to the promoter regions of target genes and regulate their expression (Ciccarelli et al, 2011;Larsen et al, 2020;Henley and Koehler, 2021;Tang et al, 2021;de Mattos et al, 2022;Xiao et al, 2022;Jiang and Qian, 2023;Yu et al, 2023;Zhao et al, 2023). Transcription factors can regulate arrhythmogenesis by modulating the expression of genes involved in the cardiac conduction system and/or myocardial structures, as well as through indirect effects on ionic currents, calcium homeostasis, inflammation, oxidative stress, and cardiac remodeling (Liang et al, 2015;Lu et al, 2015;Crespo-Garcia et al, 2022).…”

Section: Editorial On the Research Topic Transcription Factors And Ar...mentioning

confidence: 99%

Editorial: Transcription factors and arrhythmogenesis

et al. 2023

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“…[16] A variety of ion channels and receptor systems and transcription factors are involved in the pathogenesis of various types of arrhythmias. [17,18] A good example of using the multitargeting analysis of drugs in relation to the cardiovascular system is the CiPA (Comprehensive in vitro Proarrhythmia Assay) approach created for proarrhythmia risk prediction. This approach postulates the considering a comprehensive assessment of the interaction of potential drugs with an extensive set of cardiac ion channels to assess its safety and ability to initiate arrhythmias.…”

Section: Cvd and Multitargetingmentioning

confidence: 99%

Multitargeting in cardioprotection: An example of biaromatic compounds

Mokrov

2023

Archiv der Pharmazie

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A multitarget drug design approach is actively developing in modern medicinal chemistry and pharmacology, especially with regard to multifactorial diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases. A detailed study of many well‐known drugs developed within the single‐target approach also often reveals additional mechanisms of their real pharmacological action. One of the multitarget drug design approaches can be the identification of the basic pharmacophore models corresponding to a wide range of the required target ligands. Among such models in the group of cardioprotectors is the linked biaromatic system. This review develops the concept of a “basic pharmacophore” using the biaromatic pharmacophore of cardioprotectors as an example. It presents an analysis of possible biological targets for compounds corresponding to the biaromatic pharmacophore and an analysis of the spectrum of biological targets for the five most known and most studied cardioprotective drugs corresponding to this model, and their involvement in the biological effects of these drugs.

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Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias

Cited by 5 publications

References 237 publications

Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility

Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility

Editorial: Transcription factors and arrhythmogenesis

Multitargeting in cardioprotection: An example of biaromatic compounds

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