PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation

Ezeani, Martin; Prabhu, Sandeep

doi:10.1007/s11010-022-04526-w

Cited by 7 publications

(4 citation statements)

References 98 publications

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“…In non-obese patients, LA enlargement is possibly merely a consequence of prolonged hemodynamic stress due to heterogeneous conditions with LA pressure or volume overload, that can be also aggravated by atrial stand-still during AF episodes. On the other hand, genetic factors promoting LA enlargement and AF have also been identified (36,37). However, LA enlargement in obese patients seems to carry a higher propensity for AF compared to non-obese patients, which highlights the additional proarrhythmogenic impact of local and systemic inflammatory condition mediated by obesity.…”

Section: Discussionmentioning

confidence: 99%

Left Atrial Volume Predicts Atrial Fibrillation Recurrence after Catheter Ablation Only in Obese Patients

Naji,

Alatic,

Balevski

et al. 2024

Preprint

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BACKGROUND: It has been shown that obesity and higher body mass index (BMI) are associated with higher recurrence rate of atrial fibrillation (AF) after successful catheter ablation (CA). The same has been proven for left atrial volume index (LAVI). It has also been shown that there is a correlation between LAVI and BMI. However, whether LAVI prognostic impact on AF recurrence is BMI independent, remains unclear. METHODS: We prospectively included 62 patients with paroxysmal AF who were referred to our institution for CA. All patients underwent radiofrequency CA with standard pulmonary veins isolation. Transthoracic 2-D echocardiography was performed one day after CA to obtain standard measures of cardiac function and morphology. Recurrence was defined as documented AF within 6 months of follow-up period. Patients were also instructed to visit outpatient clinic earlier in case of symptoms suggesting AF recurrence. RESULTS: We observed AF recurrence in 27% of patients after 6 months. The mean BMI in our cohort was 29.65 ± 5.08 kg/cm2 and the mean LAVI was 38.04 ±11.38 ml/m2. We further divided patients into 2 groups according to BMI. Even though LAVI was similar in both groups, we found it to be significant predictor of AF recurrence only in obese patients (BMI ≥ 30), but not in the non-obese group (BMI < 30). There was also no significant difference in AF recurrence between both cohorts. The significance of LAVI as AF recurrence predictor in obesity group was also confirmed in multivariate model. CONCLUSION: According to our results LAVI tends to be significant predictor of AF recurrence after successful catheter ablation in obese patients, but not in normal-weight and overweight patients. This would suggest different mechanisms of AF in non-obese patients in comparison to the obese. Further studies are needed in this regard.

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Section: Discussionmentioning

confidence: 99%

Left Atrial Volume Predicts Atrial Fibrillation Recurrence after Catheter Ablation Only in Obese Patients

Naji,

Alatic,

Balevski

et al. 2024

Preprint

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“…Recent studies have shown that spontaneous arrhythmogenic "calcium waves" can result from genetic mutations of RyR2 but are more often due to an increase in the time of its open state [61][62][63][64][65]. Defects in its modular coupling with regulatory proteins of the cytosol, such as CaM, Epacl, PDE, FKBP12.6, PKA, PP1, calstabin, etc., or with Ca 2+ -binding proteins localized in the lumen of the SR (junctin, triadin, and calsequestrin), form temporary macromolecular complexes and can lead to a disruption of the RyR2 gate function [62,[66][67][68][69].…”

Section: Cardiac Ryanodine Receptor (Ryr2)mentioning

confidence: 99%

The Dysfunction of Ca2+ Channels in Hereditary and Chronic Human Heart Diseases and Experimental Animal Models

Shemarova

2023

IJMS

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Chronic heart diseases, such as coronary heart disease, heart failure, secondary arterial hypertension, and dilated and hypertrophic cardiomyopathies, are widespread and have a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction, and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci, and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of heart diseases are associated with impaired permeability and excitability of cell membranes and are mainly caused by the dysfunction of cardiac Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo and in situ. In this review, I discuss the origin of genetic Ca2+ channelopathies of L- and T-type voltage-gated calcium channels in humans and the role of the non-genetic dysfunctions of Ca2+ channels of various types: L-, R-, and T-type voltage-gated calcium channels, RyR2, including Ca2+ permeable nonselective cation hyperpolarization-activated cyclic nucleotide-gated (HCN), and transient receptor potential (TRP) channels, in the development of cardiac pathology in humans, as well as various aspects of promising experimental studies of the dysfunctions of these channels performed on animal models or in vitro.

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“…Ragab et al reported an increased risk of developing AF in individuals with a parental history of AF 8 . In addition, based on molecular studies, it was found that the abnormal expression of PI3Ks , SLC7A11 , CXCL12 , and other genes participated in the pathogenesis of AF 9–11 . Therefore, understanding the regulatory genes of AF can aid in early identification of individuals at high risk for developing AF.…”

Section: Introductionmentioning

confidence: 99%

“… 8 In addition, based on molecular studies, it was found that the abnormal expression of PI3Ks , SLC7A11 , CXCL12 , and other genes participated in the pathogenesis of AF. 9 , 10 , 11 Therefore, understanding the regulatory genes of AF can aid in early identification of individuals at high risk for developing AF. HF is a cardiovascular disease characterized by symptoms such as fatigue, significantly reduced exercise endurance, oedema, and paroxysmal nocturnal dyspnoea.…”

Section: Introductionmentioning

confidence: 99%

Identification of common mechanisms and biomarkers of atrial fibrillation and heart failure based on machine learning

Zhang,

Ding,

et al. 2024

ESC Heart Failure

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AimsAtrial fibrillation (AF) is the most common arrhythmia. Heart failure (HF) is a disease caused by heart dysfunction. The prevalence of AF and HF were progressively increasing over time. The co‐existence of AF and HF presents a significant therapeutic challenge. In order to provide new ideas for the diagnosis of AF and HF, it is necessary to carry out biomarker related studies.Methods and resultsThe training set and validation set data of AF and HF patient samples were downloaded from the GEO database, ‘limma’ was used to compare the differences in gene expression levels between the disease group and the normal group to screen for differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) identified the modules with the highest positive correlation with AF and HF. Functional enrichment and PPI network construction of key genes were carried out. Biomarkers were screened by machine learning. The infiltration of immune cells in AF and HF groups was evaluated by R‐packet ‘CIBERSORT’. The miRNA network was constructed and potential therapeutic agents for biomarker genes were predicted through the drugbank database. Through WGCNA analysis, it was found that the modules most positively correlated with AF and HF were MEturquoise (r = 0.21, P value = 0.09) and MEbrown (r = 0.62, P value = 8e‐12), respectively. We screened 25 genes that were highly correlated with both AF and HF. Lasso regression analysis results showed 7 and 20 core genes in AF and HF groups, respectively. The top 20 important genes in AF and HF groups were obtained as core genes by RF model analysis. Four biomarkers were obtained after the intersection of core genes in four groups, namely, GLUL, NCF2, S100A12, and SRGN. The diagnostic efficacy of four genes in AF validation sets was good (AUC: GLUL 0.76, NCF2 0.64, S100A12 0.68, and SRGN 0.76), as well as in the HF validation set (AUC: GLUL 0.76, NCF2 0.84, S100A12 0.92, and SRGN 0.68). The highest correlation with neutrophils was observed for GLUL, NCF2, and S100A12, while SRGN exhibited the strongest correlation with T cells CD4 memory resting in the AF group. GLUL, NCF2, S100A12, and SRGN were most associated with neutrophils in the HF group. A total of 101 miRNAs were predicted by four genes, and GLUL, NCF2, and S100A12 predicted a total of 10 potential therapeutic agents.ConclusionsWe identified four biological markers that are highly correlated with AF and HF, namely, GLUL, NCF2, S100A12, and SRGN. Our findings provide theoretical basis for the clinical diagnosis and treatment of AF and HF.

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PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation

Cited by 7 publications

References 98 publications

Left Atrial Volume Predicts Atrial Fibrillation Recurrence after Catheter Ablation Only in Obese Patients

Left Atrial Volume Predicts Atrial Fibrillation Recurrence after Catheter Ablation Only in Obese Patients

The Dysfunction of Ca2+ Channels in Hereditary and Chronic Human Heart Diseases and Experimental Animal Models

Identification of common mechanisms and biomarkers of atrial fibrillation and heart failure based on machine learning

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