Vascular homeostasis depends on coordinated responses among endothelial cells, vascular smooth muscle cells, and perivascular cells. The Hippo pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) integrate mechanical, metabolic, and biochemical cues within these cell types. Their effects are highly context-dependent, supporting vascular development and integrity under physiological conditions while promoting inflammation, maladaptive remodeling, or calcification in specific disease settings. This review synthesizes the regulatory networks that control YAP/TAZ across vascular cell types and examines their roles in atherosclerosis, angiogenesis, vascular calcification, and related disorders. We further assess emerging YAP/TAZ-directed therapies and define the central translational challenge: achieving cell-, site-, and stage-specific modulation without disrupting essential homeostatic and regenerative functions.
Aim: Mitochondrial DNA (mtDNA) methylation is an emerging epigenetic regulator of mitochondrial function, yet the mechanisms governing its dynamic regulation under cellular stress—particularly in the heart—remain poorly understood. This study aimed to investigate whether aldehyde dehydrogenase 2 (ALDH2) regulates mtDNA methylation via the mitochondrial targeting of DNA methyltransferase 1 (DNMT1) during myocardial ischemia, and to explore the functional consequences of this regulation in Ischemic heart disease (IHD). Methods: We identified a specific DNMT1 isoform containing a mitochondrial targeting sequence (MTS) and confirmed its localization to cardiomyocyte mitochondria. Myocardial infarction (MI) was induced in wild-type and ALDH2-knockout mice. Mitochondrial DNMT1 levels, mtDNA 5-methylcytosine (5mC) content, and MTS expression were assessed at various post-MI time points. Site-specific mtDNA methylation at ND1 and ND2 loci was analyzed. Hypoxia experiments in cardiomyocytes were performed to evaluate ALDH2-dependent DNMT1 translocation, mitochondrial gene expression, and respiratory capacity. Post-MI cardiac function was assessed by echocardiography. Results: We confirm that a specific DNMT1 isoform localizes to cardiomyocyte mitochondria via its MTS and modulates mtDNA 5mC levels. Following MI, mitochondrial DNMT1 levels and mtDNA methylation exhibited a biphasic response: an initial increase during the early ischemic phase (1 week post-MI), followed by a decline in the later remodeling phase. Genetic deletion of ALDH2 impaired mitochondrial translocation of DNMT1, associated with downregulated MTS expression and reduced global mtDNA 5mC. Site-specific analysis revealed that ALDH2 deficiency significantly altered methylation patterns at the ND1 and ND2 loci. Functionally, hypoxia inhibited DNMT1 mitochondrial translocation in an ALDH2-dependent manner, thereby modulating the expression of these mitochondrial-encoded genes and overall mitochondrial respiratory capacity. Importantly, ALDH2 deficiency exacerbated post-MI cardiac dysfunction. Conclusion: Our findings uncover a novel regulatory axis in which ALDH2 fine-tunes the dynamic equilibrium of mtDNA methylation by governing DNMT1-MTS expression, offering mechanistic insight into mitochondrial epigenetic adaptation in IHD and a potential therapeutic target for ALDH2-deficient populations.
Coronary artery fistulas are rare vascular anomalies that may cause chronic left-to-right shunting, cardiac chamber remodeling, and heart failure. We report a 72-year-old woman with a left main coronary artery-to-right atrium fistula draining through a giant aneurysmal atrial septal artery and accompanied by severe secondary mitral regurgitation. Echocardiography and cardiac computed tomography showed a 19 mm fistulous tract, a 31 × 30 mm aneurysmal vascular structure with a 5 mm outlet to the right atrium, and severe mitral regurgitation with an effective regurgitant orifice area of 0.56 cm2 and a regurgitant volume of 89 mL. Owing to high surgical risk and complex septal anatomy, a staged transcatheter strategy was adopted. The fistula was first closed using an AMPLATZER VASCULAR PLUG II and coil embolization, with satisfactory occlusion and mild residual flow. Two months later, mitral regurgitation worsened despite medical therapy. A three-dimensional printed model was used to plan a safe transseptal puncture trajectory, and transcatheter edge-to-edge repair was performed with two MitraClip XTR devices. Mitral regurgitation was markedly reduced, with sustained symptomatic, echocardiographic, and biomarker improvement at 12 months. This case suggests that sequential transcatheter fistula closure and mitral valve repair, supported by multimodality imaging and three-dimensional printing, may be feasible in carefully selected high-risk patients with complex coronary fistula anatomy and severe mitral regurgitation.
Heart failure (HF) is a type of chronic pathological remodeling in which the heart fails to efficiently supply an adequate amount of blood to fulfill the body’s requirements. Circular RNAs (circRNAs) are recognized as specific types of long noncoding RNAs that are involved in the regulation of the pathogenesis of cardiovascular diseases, including cardiac remodeling and HF. In this review, knowledge about the origin, characteristics, and function of circRNAs is summarized. The regulatory function of circRNAs in cardiac remodeling mechanisms, including cell death, cardiac hypertrophy, fibrosis and mitochondrial metabolism, is reviewed. Finally, future directions for investigating the diagnostic and pharmacological potential of circRNAs in HF are proposed.
With population aging and the rising incidence of cardiac disease, interventional cardiology, as a cornerstone of treatment for conditions such as coronary and structural heart disease, faces persistent challenges, including stringent precision requirements, heavy reliance on operator experience, and variability in diagnostic and therapeutic efficiency. With robust capabilities in data mining, image recognition, real-time analysis, and predictive modeling, artificial intelligence (AI) offers a novel pathway to address the aforementioned challenges and support the intelligent transformation of interventional cardiology. This narrative review briefly outlines the background to the application of AI in interventional cardiology, focuses on core supporting technologies including deep learning, machine learning, and computer vision, and summarizes current research and clinical applications of AI across preprocedural risk assessment and planning, intraprocedural real-time navigation and early warning of complications, and postprocedural follow-up and prognosis prediction. It also analyzes the principal challenges currently facing AI in this field, such as data quality and security issues, insufficient algorithm interpretability, barriers to clinical translation, and constraints from ethical and regulatory frameworks. Finally, in light of technological advances and clinical needs, this review outlines future directions, including the integration of AI with interventional devices, multimodal data integration and modeling, and the development of personalized interventional strategies, thereby providing a reference for promoting the standardized and large-scale application of AI technology in interventional cardiology.
