Cathepsin B (CatB) is a cysteine proteolytic enzyme widely expressed in various cells and mainly located in the lysosomes. It contributes to the pathogenesis and development of many diseases. However, the role of CatB in viral myocarditis (VMC) has never been elucidated. Here we generated the VMC model by intraperitoneal injection of coxsackievirus B3 (CVB3) into mice. At day 7 and day 28, we found CatB was significantly activated in hearts from VMC mice. Compared with the wild-type mice receiving equal amount of CVB3, genetic ablation of CatB (Ctsb^-/-) significantly improved survival, reduced inflammatory cell infiltration, decreased serum level of cardiac troponin I, and ameliorated cardiac dysfunction, without altering virus titers in hearts. Conversely, genetic deletion of cystatin C (Cstc^-/-), which markedly enhanced CatB levels in hearts, distinctly increased the severity of VMC. Furthermore, compared with the control, we found the inflammasome was activated in the hearts of wild-type mice with VMC, which was attenuated in the hearts of Ctsb^-/- mice but was further enhanced in Cstc^-/- mice. Consistently, the inflammasome-initiated pyroptosis was reduced in Ctsb^-/- mice hearts and further increased in Cstc^-/- mice. These results suggest that CatB aggravates CVB3-induced VMC probably through activating the inflammasome and promoting pyroptosis. This finding might provide a novel strategy for VMC treatment. Severe VMC could lead to sudden cardiac death especially in youths, and is also the most common cause of secondary dilated cardiomyopathy. However, we still lack effective and specific clinical treatments currently. Therefore, further exploration of the pathogenesis and new therapeutic targets are urgently needed. Our results implied that CatB, a cysteine protease mainly located in the lysosome, is activated in the hearts of mice with VMC induced by intraperitoneal injection of CVB3. Genetic deletion of CatB significantly improves survival, attenuates cardiac inflammation, decreases serum cardiac troponin I levels and alleviates cardiac dysfunction, without altering virus titers in hearts. However, ablation of its main endogenous inhibitor, cystatin C, distinctly exaggerates the disease severity. Mechanistically, we found that CatB influences VMC probably by activating the NLRP3 inflammasome and promoting caspase-1-induced pyroptosis. This may provide a potential new therapeutic strategy for VMC.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell–specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg ). Pik3cg ablation hindered AAA progression, and myeloid cell–specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.

Kounis syndrome, defined as an acute coronary syndrome triggered by allergic or hypersensitivity reactions, is a rare yet potentially life-threatening condition. This report details the case of a 50-year-old female patient presenting with recurrent chest pain, hypereosinophilia, and allergic comorbidities, who was ultimately diagnosed with type I Kounis syndrome. Modifications to her treatment regimen, including the administration of diltiazem and prednisolone, led to a complete resolution of her symptoms. This case highlights the critical importance of early diagnosis and timely intervention in managing Kounis syndrome. Early recognition is essential to prevent potentially fatal outcomes, thereby emphasizing the need for increased awareness among healthcare professionals.

Cardiovascular toxicity associated with anti-tumor therapies is garnering increased attention. Anti-tumor therapies may elevate the risk of acute coronary syndrome, particularly in patients with underlying subclinical atherosclerosis. In this context, a 58-year-old female patient with HER2-positive breast cancer experienced an acute ST-segment elevation myocardial infarction following chemotherapy, dual HER2-targeted therapy, and radiotherapy to the left breast. Prior to the initiation of anti-tumor treatment, chest-computed tomography had identified coronary artery calcification. Angiographic evaluation revealed subtotal occlusion of the middle segment of the left circumflex artery extending to the first obtuse marginal branch, accompanied by multivessel coronary atherosclerotic lesions. Coronary blood flow was restored following emergency interventional treatment. This case indicates that multimodal anti-tumor therapy may facilitate the progression of coronary atherosclerosis, thereby elevating the risk of acute coronary events.

Advances in anticancer therapies have substantially improved cancer survival but have also highlighted the growing challenge of cancer therapy-related cardiac dysfunction. Ferroptosis, an iron-dependent form of regulated cell death characterized by iron dysregulation, lipid peroxidation, and impaired antioxidant defense, has emerged as a promising strategy for eliminating therapy-resistant tumors. However, the lack of tissue specificity in ferroptosis regulation raises concerns regarding its potential contribution to cardiovascular injury during anticancer treatment. This review summarizes the dual roles of ferroptosis in cancer biology and cardio-oncology. We first discuss the molecular mechanisms governing ferroptosis, including iron metabolism, lipid peroxidation, and antioxidant defense systems. We then highlight the context-dependent roles of ferroptosis in tumor progression, immune regulation, and metabolic adaptation. Furthermore, we systematically review how chemotherapy, targeted therapy, immunotherapy, and radiotherapy contribute to ferroptosis-associated cardiovascular toxicity. Finally, we discuss emerging approaches to minimize cardiac injury, including tissue-specific ferroptosis-targeting and cardioprotective strategies. Understanding tissue-specific ferroptosis regulation may facilitate the development of safer and more precise therapeutic approaches in cardio-oncology.