Both hypertension and sleep disturbance have been closely linked to inflammation. However, the specific role of inflammation in the relationship between sleep disturbance and hypertension remains unclear. We investigated the pairwise associations among a novel inflammatory marker (systemic immune inflammation index ), sleep disturbance, and hypertension in a powerful, racially diverse sample (n = 23,414) from the 2005–2020 National Health and Nutrition Examination Survey (NHANES). We found that participants with high blood pressure and/or sleep disorders had higher levels of Systemic Immune-Inflammatory Index (SII) than those without hypertension or sleep disorders.SII slightly but significantly mediated the relationship between sleep disturbance and hypertension in males but not in females, after adjusting for all covariates (proportion mediate [PM], 1.36%; total effect [TE], 0.0931; direct effect [ADE], 0.0917; verage causal mediation effects [ACME] = 0.0013 [95% CI = 0.0004–0.0024], p = 0.002, in males. Our research showed that SII, sleep disturbance, and hypertension are related. Increased SII levels slightly mediated the association between sleep disturbance and hypertension.

Introduction: Hypertensive heart disease (HHD) is characterized by chronic pressure overload leading to myocardial remodeling and fibrosis. While inflammation and cell death pathways contribute to fibrogenesis, the mechanistic role of neutrophil extracellular traps (NETs) remains insufficiently understood. This study investigated whether NETs exacerbate myocardial fibrosis in spontaneously hypertensive rats (SHRs) through activation of the nuclear factor-κB (NF-κB) signaling pathway and ferroptosis. Methods: Male SHRs and normotensive Wistar-Kyoto (WKY) rats were used to assess blood pressure, cardiac function, and myocardial fibrosis via echocardiography, histology, and Western blotting. Transcriptomic profiling, immunofluorescence, and ELISA quantified NET-associated and ferroptosis-related markers. H9c2 cardiomyoblasts were treated with angiotensin II (Ang II) or isolated NETs, with or without DNase I, Ferrostatin-1 (Fer-1, ferroptosis inhibitor), or JSH-23 (NF-κB inhibitor). Gene and protein expression were analyzed by qPCR and Western blotting to elucidate NET-induced molecular mechanisms. Results: SHRs exhibited elevated systolic blood pressure, reduced ejection fraction, and marked myocardial fibrosis with increased collagen deposition. Transcriptomic and proteomic analyses revealed significant upregulation of NETs and ferroptosis-related genes, accompanied by NF-κB pathway enrichment. Myocardial and serum levels of citrullinated histone H3 and myeloperoxidase were elevated, confirming enhanced NET formation. In H9c2 cells, NETs induced ferroptotic features—elevated ACSL4, reduced FTH1 and GPX4—and activated NF-κB signaling, leading to increased expression of α-SMA, fibronectin, collagen II, and MMP3. DNase I pretreatment or inhibition of ferroptosis or NF-κB each mitigated these changes, with combined inhibition exerting the strongest suppressive effect. Discussion: These findings identify a pathogenic NETs/NF-κB/ferroptosis axis that drives hypertensive myocardial fibrosis. NETs promote oxidative stress and iron-dependent cell death in cardiomyocytes, amplifying inflammatory and profibrotic signaling. Therapeutic targeting of NETs formation or downstream ferroptotic and NF-κB pathways may thus attenuate fibrotic remodeling and preserve cardiac function in HHD. This study provides mechanistic insight into how sterile inflammation orchestrates myocardial injury and highlights novel intervention strategies against hypertensive cardiac fibrosis.

Atrial fibrillation (AF), the most prevalent clinical atrial arrhythmia, arises from complex dysregulation of multicellular signalling pathways and molecular networks. Recent advances in cardiac electrophysiology have identified the atrial-specific gap junction protein Connexin 40 (Cx40) as a pivotal regulator of intercellular communication and cardiac electrical synchronization in AF pathogenesis. Aberrant Cx40 expression significantly disrupts atrial electrical conduction, yet its precise regulatory mechanisms remain incompletely understood. This review systematically examines the multifaceted roles of Cx40 in AF development, particularly focusing on how Cx40 genetic polymorphisms influence cardiac electrophysiology and promote atrial structural remodelling. Furthermore, we elucidate the ubiquitination-mediated protein degradation pathways governing Cx40 stability. These insights advance our understanding of AF pathophysiology and highlight potential therapeutic targets for precision arrhythmia management.

Myocardial ischemia-reperfusion (MI/R) injury frequently occurs during the clinical management of ischemic heart disease. The underlying mechanism includes neutrophil infiltration, heightened intracellular Ca²⁺ levels, mitochondrial energy metabolism disorder. This study investigated the pathological role of the inositol 1,4,5-trisphosphate receptor/mitochondrial calcium uniporter (ITPR1/MCU) pathway in regulating disturbances in intracellular calcium ([Ca²⁺]_i) and mitochondrial calcium ([Ca²⁺]_m) levels during MI/R injury. Furthermore, the study explored the potential of 2-aminoethoxydiphenylborane (2-APB) as a cardioprotective agent against MI/R injury. The outcomes of this investigation demonstrated that the ITPR1/MCU pathway was activated after MI/R, leading to [Ca²⁺]_i/[Ca²⁺]_m overload, impairing mitochondrial structure and function, and promoting cardiomyocyte death. The administered treatment attenuates myocardial injury after MI/R by reversing the [Ca²⁺]_i/[Ca²⁺]_m imbalance, maintaining cardiomyocyte mitochondrial homeostasis and promoting cardiomyocyte survival. Furthermore, the administration of 2-APB exerted a suppressive effect on MCU expression. Notably, the activation of MCU abolished the cardioprotective impact mediated by 2-APB. These results suggest that 2-APB intervenes [Ca²⁺]_i/[Ca²⁺]_m balance and maintains mitochondrial function through the ITPR1/MCU pathway. The strategic manipulation of this pathway holds promise as a prospective avenue for the clinical treatment of MI/R injury.

Genome-wide association studies (GWAS) have identified loci associated with alcohol-related hepatocellular carcinoma (ALD-HCC); however, most risk variants

Mitochondrial Antiviral Signaling Protein (MAVS) is a pivotal adaptor protein in the innate immune response, mediating the activation of NF-κB and type I interferon signaling pathways during viral infections. As an integral component of the mitochondrial outer membrane, MAVS also plays critical roles in the regulation of apoptosis, cellular metabolism, and the activation of inflammasomes, including NLRP3 and caspase family members. Emerging evidence indicates that MAVS is not only essential in antiviral defense but also contributes significantly to the pathogenesis of various diseases, notably cardiovascular diseases. In this review, we provide a comprehensive overview of the molecular structure of MAVS and the regulatory mechanisms modulating its activity. We further highlight the involvement of MAVS in the development of cardiovascular diseases through its participation in innate immune signaling and mitochondrial dynamics. Particular attention is given to the regulation of MAVS by post-translational modifications—such as ubiquitination, methylation, and acetylation—as well as by microRNAs and other mitochondria-associated proteins. These insights aim to deepen the understanding of MAVS as a potential biomarker and therapeutic target, offering novel perspectives for the prevention, diagnosis, and immunotherapeutic intervention of cardiovascular diseases.