Hyperhomocysteinemia (HHcy) can be used as an independent risk factor for predicting cardiovascular disease, stroke and vitamin B12 deficiency. Patients with HHcy have elevated plasma homocysteine (Hcy) concentrations. Enhancing cerebrovascular permeability of substances such as Hcy and brain damage will synergistically increase the symptoms of hypertension, but the specific immune regulation mechanism is still not clear. The purpose of the present study was to preliminarily explore the immunomodulatory mechanism of brain damage caused by HHcy in Wistar‑Kyoto (WKY) rats. A total of 60 WKYs were randomly divided into three groups: WKY control group (WKY‑C group), WKY methionine group (WKY‑M group) and WKY treatment group (WKY‑T group; vitamin B6, B12 and folic acid were used as treatment), with 20 rats in each group. Physical examination of body weight, systolic blood pressure (SBP) and plasma Hcy content was performed routinely. The concentration of cytokines, including IL‑6, IL‑10, IL‑17A and TGF‑β, associated with T helper cell 17 (Th17) and regulatory T (Treg) cells and key regulator genes, including retinoic acid‑related orphan receptor γ t (RORγt) and forkhead box P3 (FoxP3), were detected by ELISA, reverse transcription‑quantitative PCR and western blotting. Th17/Treg lymphocytes were determined by flow cytometry. MRI scan was preliminarily used to detect the changes characteristic of the ischemic stroke. The results revealed that high methionine diets might have a significant effect on the body weight and SBP. The inflammatory response effect of Treg cells was significantly inhibited in the WKY‑M group, and that of Th17 cells was upregulated when compared to the WKY‑T group. Compared with the WKY‑T group, the expression levels of IL‑17A and RORγt in the WKY‑M group were significantly upregulated, while the mRNA levels of FoxP3 in the WKY‑M group were significantly downregulated. The diet intervention (including vitamins B6 and B12 and folic acid) could reduce the level of Hcy in the blood, but also reduce the inflammatory response and rectify the Treg/Th17 immune imbalance to ameliorate the brain tissue damage. In conclusion, the present study indicated that HHcy can promote inflammation by triggering Treg/Th17 immune imbalance to ameliorate the brain tissue damage.

Fabry disease (FD) is a rare X chromosome‐linked disorder and can be easily misdiagnosed. Here, we report the case of a 69‐year‐old male patient with FD who developed heart failure and showed extremely high pulmonary artery pressure. His initial symptom was recurrent atrial fibrillation. The left and right atrial inner diameters were large, and the ventricular wall was thick. Gene analysis which showed GLA c.215T>C p.Met72Thr mutation and single photon emission computed tomography indicated the diagnosis of FD with coronary microvascular dysfunction. The patient was prescribed anti‐heart failure drugs, including vericiguat. Following the treatment, his heart function and microvascular perfusion significantly improved, which might be due to the beneficial effects of vericiguat.

Genetic factors are estimated to cause approximately 30%–50% of dilated cardiomyopathy (DCM) cases, with Titin (TTN) being the most commonly implicated gene, accounting for 20%–25% of genetic causes. Many DCM-causing TTN mutations are heterozygous truncating variants, including frameshift, non-sense, and essential splice site mutations. SCN5A mutations are associated with arrhythmias, while pathogenic variants in the low-density lipoprotein receptor (LDLR) gene are associated with familial hypercholesterolemia. Here, we report a case of DCM with a novel TTN variant, as well as two rare variants in the SCN5A and LDLR genes. It is rare for a patient to have three rare genetic variations and this may expand the genetic map of DCM and TTN, offering important insights for future studies on their genetic and disease relationships.

Type A aortic dissection (TAAD) is a vascular disease with high mortality; however, the role of gene methylation in its pathogenesis has received little attention. This study aimed to identify candidate markers of TAAD by integrating methylation and transcriptome sequencing analyses. Aortic tissue samples from five TAAD cases and five controls were sequenced on Illumina Hiseq sequencing platform and Infinium Methylation EPIC BeadChip microarray. A series of bioinformatics analyses and machine learning algorithms were used to identify key methylated genes from the differentially expressed genes and differentially methylated sites between TAAD and controls. An overexpression vector of ZC3H12A was constructed, and human vascular smooth muscle cells (HVSMCs) were transfected with the vector to explore the effects of key methylated genes on cell proliferation, migration, and phenotypic switch. Differential analysis and integration of gene expression and methylation levels between TAAD and control samples suggested 239 differentially methylated genes, mainly involved in nicotinamide nucleotide biosynthetic and metabolic processes. By applying protein-to-protein network and machine learning algorithms, we finally identified three methylated genes, including ZC3H12A, IRAK2, and CCL5, which could be used as potential markers of TAAD. Both correlation analysis and experimental validation results indicated that expression levels of these genes were significantly negatively regulated by their methylation levels. Among them, ZC3H12A was confirmed to significantly promote the proliferation and migration in HVSMCs in vitro, while inhibiting their phenotypic transformation. Three methylated genes were identified as potential diagnostic markers for TAAD. Among them, ZC3H12A might contribute to disease progression.