Background: Cardiac remodeling predisposes individuals to heart failure if the burden is not solved, and heart failure is a growing cause of morbidity and mortality worldwide. The cardiac extracellular matrix not only provides structural support, but also is a core aspect of the myocardial response to various biomechanical stresses and heart failure. MFAP4 (microfibrillar‐associated protein 4) is an integrin ligand located in the extracellular matrix, whose biological functions in the heart remain poorly understood. In the current study we aimed to test the role of MFAP4 in cardiac remodeling. Methods and Results: MFAP4‐deficient (MFAP4 ^−/− ) and wild‐type mice were subjected to aortic banding surgery and isoproterenol to establish models of cardiac remodeling. We also evaluated the functional effects of MFAP4 on cardiac hypertrophy, fibrosis, and cardiac electrical remodeling. The expression of MFAP4 was increased in the animal cardiac remodeling models induced by pressure overload and isoproterenol. After challenge of 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol, MFAP4 ^−/− mice exhibited lower levels of cardiac fibrosis and fewer ventricular arrhythmias than wild‐type mice. However, there was no significant effect on cardiomyocyte hypertrophy. In addition, there was no significant difference in cardiac fibrosis severity, hypertrophy, or ventricular arrhythmia incidence between wild‐type‐sham and knockout‐sham mice. Conclusions: These findings are the first to demonstrate that MFAP4 deficiency inhibits cardiac fibrosis and ventricular arrhythmias after challenge with 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol but does not significantly affect the hypertrophy response. In addition, MFAP4 deficiency had no significant effect on cardiac fibrosis, hypertrophy, or ventricular arrhythmia in the sham group in this study.

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'‐deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress‐dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after‐surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91^phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin‐treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post‐AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.

Aims: Ventricular arrhythmias (VAs), which can lead to sudden cardiac death, are the primary cause of mortality in patients with heart failure (HF). However, the precise mechanisms underlying these arrhythmias are not well understood. Recent studies have implicated tumour necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in pathological cardiac hypertrophy. Nevertheless, its role in isoproterenol (ISO)-associated VAs remains elusive. Methods and results: We overexpressed TNIP3 in the myocardium using an adeno-associated virus 9 system, administered via tail vein injection. C57BL/6 mice received daily subcutaneous injections of ISO for two consecutive weeks to establish an HF model. We performed histopathology and electrophysiological studies to assess ventricular structural remodelling, electrical remodelling, and susceptibility to VAs. Additionally, RNA sequencing (RNA-Seq) and western blot analysis were conducted to elucidate the underlying mechanisms. The expression of TNIP3 was up-regulated following ISO treatment. TNIP3 overexpression significantly reversed ISO-induced cardiac dysfunction, fibrosis, electrical remodelling, and VAs susceptibility. Accordingly, RNA-Seq identifies that the inflammatory response takes an important role in ISO-induced Vas, and TNIP3 overexpression could alleviate ISO-induced cardiac proinflammatory response by promoting M1 to M2 macrophage polarization. Mechanistically, PI3K/Akt/NF-κB signalling is responsible for the protective effect of TNIP3 overexpression on ISO-induced HF. And PI3K/Akt signalling activation offset the protective effect of TNIP3 overexpression on ISO-induced cardiac inflammation and VAs. Conclusion: The findings of this study highlight the critical role of TNIP3 in ISO-associated cardiac remodelling and VAs, which are induced by the inhibited activation of the PI3K/Akt/NF-κB signalling pathway.

Oxidative stress and inflammation are common medical issues contributing to the onset and progression of heart failure (HF). Sulfiredoxin 1 (Srxn1) is a key regulatory factor in the antioxidant response. This study aimed to examine the effect of Srxn1 in HF. We utilised transcriptome sequencing to screen for differentially expressed genes in cardiac remodelling. We overexpressed Srxn1 in the hearts using an adeno‐associated virus 9 (AAV9) system through tail vein injection. C57BL/6 mice were subjected to transverse aortic constriction (TAC) for 4 weeks. Echocardiography was used to evaluate cardiac function, and cardiac remodelling was estimated by histopathology and molecular techniques. In addition, H9C2 cells were stimulated by Ang II to establish an in vitro model of cardiomyocyte hypertrophy, and the effects of Srxn1 overexpression on the inflammatory pathways and oxidative stress in Ang II‐stimulated H9C2 cells were examined. We found that Srxn1 is downregulated after cardiac remodelling by transcriptome sequencing. Our results revealed down‐regulated levels of Srxn1 in murine hearts subjected to TAC treatment, and H9C2 challenged with Ang II. Moreover, compared with WT mice, AAV‐9‐Srxn1 mice exhibited dramatically ameliorated TAC‐induced cardiac dysfunction, hypertrophy, fibrosis, oxidative stress, and inflammation. In terms of mechanism, both in vitro and in vivo experiments confirmed that the potential positive impacts may be linked to the inhibition of TLR4/NF‐κB signalling. In summary, this study is the first to demonstrate the protective effects of Srxn1 against TAC‐induced cardiac oxidative stress and inflammation, which are induced by the inhibited activation of the TLR4/NF‐κB signalling pathway.

Rationale: Turner syndrome is characterized by complete or partial loss of the second sex chromosome. In patients with Turner syndrome, hypertension is well described. However, the literature regarding malignant hypertension is scarce. Therefore, an accurate and timely diagnosis and treatment are important. Patient concerns: A 13-year-old female with Turner syndrome presented to the emergency department with malignant hypertension, headache, spraying vomiting, convulsion, and loss of consciousness. Considering her medical history, symptoms, and auxiliary examination, secondary hypertension (primary reninism) was suspected, but without any occupying or hyperplasia in renal and adrenal. Diagnosis: A type of secondary hypertension, primary reninism. Interventions: The patient was immediately transferred to the pediatric intensive care unit. Subsequently, she was given nifedipine 0.35 mg/kg and captopril 0.35mg/kg to reduce blood pressure (BP), mannitol and furosemide to reduce cranial pressure, and phenobarbital and midazolam to terminate restlessness successively. Three hours later, the BP was consistently higher than 170/120 mm Hg, sodium nitroprusside was pumped intravenously, then, giving oral drug transition. Finally, she was given Valsartan-Amlodipine Tablets (I) (80 mg valsartan and 5 mg amlodipine per day) and bisoprolol (2.5 mg per day). Outcomes: For 2.5 years of follow-up, the BP reduced to 110–130/60–85 mm Hg, heart rate ranged between 65 and 80 bpm, and she could go to school without any headache, convulsion, and syncope. Lessons: The clinical phenotype of Turner syndrome is complex and varied, affecting multiple systems and organs. Turner syndrome with malignant hypertension is rare, so we should systematically evaluate secondary hypertension, target-organ damage, and accompanied by standard management when Turner syndrome presents with hypertension.