The effect of unhealthy lifestyle on the pathogenesis of sick sinus syndrome: A life-guiding review.

Sick sinus syndrome (SSS), also known as sinoatrial node dysfunction, has been widely concerned by the medical community. The incidence rate of SSS is increasingly, which poses a great threat to public health. Through decades of repeated research in the medical field, great progress has been made in the pathogenesis of SSS and the interaction mechanism between SSS and other cardiovascular diseases. In this paper, we pay special attention to the mental stimulation factors under various pressures such as society and work, and the influence of smoking, drinking, and unhealthy diet on the pathogenesis of SSS. It also explains the mechanism of negative factors in the pathogenesis of SSS. These unhealthy lifestyle will lead to the occurrence of sinoatrial node disease and arrhythmia, and then induce SSS. Therefore, in the premise of increasing incidence rate of SSS and difficult to cure, how to avoid these harmful factors and ensure a healthy lifestyle is extremely important for preventing and treating SSS. This study also has guiding significance for the daily life of high-risk population of SSS and reducing the mortality of SSS patients.

Genetic basis and causal relationship between atrial fibrillation and sinus node dysfunction: Evidence from comprehensive genetic analysis.

BACKGROUND: Atrial fibrillation (AF) and sinus node dysfunction (SND) are commonly observed together clinically. However, little is known about the genetic background and causal relationship between the two. METHODS: Firstly, we investigated the global and local genetic correlations between AF and SND using LDSC and HESS. Then, we identified shared "Novel SNPs" between AF and SND through two complementary cross-trait meta-analyses and mapped the "pleiotropic genes" behind these SNPs, validated by colocalization analysis. Additionally, we explored the degree of genetic enrichment of SNPs in specific tissues using LDSC-SEG and MAGMA, and identified potential functional genes in tissues using summary data-based Mendelian randomization (SMR). Finally, two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) were used to explore the causal relationship between AF and SND. RESULTS: Both global and local genetic correlation analyses revealed a high positive genetic correlation between AF and SND. HESS identified 9 shared loci, with chr4(q25-q26) and chr11(p11.12-q11) being prominent. Cross-trait meta-analysis and colocalization analysis identified ENPEP and PITX2 as novel pleiotropic genes. MAGMA revealed genetic enrichment of SNPs for AF and SND in the "Heart Left Ventricle" and "Heart Atrial Appendage" tissues, with CEP68 and BEST3 identified as potential functional genes through SMR. MR analysis indicated that AF increases the risk of SND, even after adjusting for confounding factors. CONCLUSION: This study provides genetic evidence for the increased risk of SND associated with AF, identifying multiple shared risk loci and enriched tissues, and discovering 2 novel pleiotropic genes and 2 new functional genes.

Modulating mitochondrial dynamics ameliorates left ventricular dysfunction by suppressing diverse cell death pathways after diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) triggers a detrimental shift in mitochondrial dynamics, characterized by increased fission and decreased fusion, contributing to cardiomyocyte apoptosis and cardiac dysfunction. This study investigated the impact of modulating mitochondrial dynamics on DCM outcomes and underlying mechanisms in a mouse model. DCM induction led to upregulation of fission genes (Drp1, Mff, Fis1) and downregulation of fusion genes (Mfn1, Mfn2, Opa1). Inhibiting fission with Mdivi-1 or promoting fusion with Ginsenoside Rg1 preserved cardiac function, as evidenced by improved left ventricular ejection fraction (LVEF), fractional shortening (FS), and E/A ratio. Both treatments also reduced infarct size and attenuated cardiomyocyte apoptosis, indicated by decreased caspase-3 activity. Mechanistically, Mdivi-1 enhanced mitochondrial function by improving mitochondrial membrane potential, reducing reactive oxygen species (ROS) production, and increasing ATP generation. Ginsenoside Rg1 also preserved mitochondrial integrity and function under hypoxic conditions in HL-1 cardiomyocytes. These findings suggest that restoring the balance of mitochondrial dynamics through pharmacological interventions targeting either fission or fusion may offer a promising therapeutic strategy for mitigating MI-induced cardiac injury and improving patient outcomes.

Ginsenoside Rb1 ameliorates heart failure through DUSP-1-TMBIM-6-mediated mitochondrial quality control and gut flora interactions.

BACKGROUND: There is currently no specific therapeutic drug available for heart failure in clinical practice. Numerous studies have validated the efficacy of Ginsenoside Rb1, an active component found in various herbal remedies used for heart failure treatment, in effectively ameliorating myocardial ischemia. However, the precise mechanism of action and molecular targets of Ginsenoside Rb1 remain unclear. PURPOSE: This study aims to explore the molecular mechanisms through which Ginsenoside Rb1 synergistically modulates the gut flora and mitochondrial quality control network in heart failure by targeting the DUSP-1-TMBIM-6-VDAC1 axis. STUDY DESIGN: This study utilized DUSP-1/VDAC1 knockout (DUSP-1-/-/VDAC1-/-) and DUSP-1/VDAC1 transgenic (DUSP-1+/+/VDAC1+/+) mouse models of heart failure, established through Transverse Aortic Constriction (TAC) surgery and genetic modification techniques. The mice were subsequently subjected to treatment with Ginsenoside Rb1. METHODS: A series of follow-up multi-omics analyses were conducted, including assessments of intestinal flora, gene transcription sequencing, single-cell databases, and molecular biology assays of primary cardiomyocytes, to investigate the mechanism of action of Ginsenoside Rb1. RESULTS: Ginsenoside Rb1 was found to have multiple regulatory mechanisms on mitochondria. Notably, DUSP-1 was discovered to be a crucial molecular target of Ginsenoside Rb1, controlling both intestinal flora and mitochondrial function. The regulatory effects of DUSP-1 on inflammation and mitochondrial quality control were mediated by changes in TMBIM-6 and VDAC1. Furthermore, NLRP3-mediated inflammatory responses were found to interact with mitochondrial quality control, exacerbating myocardial injury under stress conditions. Ginsenoside Rb1 modulated the DUSP-1-TMBIM-6-VDAC1 axis, inhibited the release of pro-inflammatory factors, altered the structural composition of the gut flora, and protected impaired heart function. These effects indirectly influenced the crosstalk between inflammation, mitochondria, and gut flora. CONCLUSION: The DUSP-1-TMBIM-6-VDAC1 axis, an upstream pathway regulated by Ginsenoside Rb1, is a profound mechanism through which Ginsenoside Rb1 improves cardiac function in heart failure by modulating inflammation, mitochondria, and gut flora.