Journal of Cardiovascular Translational Research最新文献

Takotsubo syndrome (TTS) is an under-recognized form of acute-onset heart failure typically precipitated by stress. While recovery of cardiac function is described over the course of weeks, adverse outcomes after apparent recovery are increasingly recognized. However, the pathophysiology of non-acute manifestations remains poorly understood. We used mass-spectrometry-based discovery proteomics from remotely collected non-acute dried blood microsamples to perform a case-control study in 62 participants with a prior TTS episode (median of 2.24 years prior to sample collection) and 47 reference controls. We quantified 398 unique proteins, and found that agnostic clustering techniques showed separation between TTS and reference control samples. This represents the first proteomic characterization of non-acute TTS. Pathway analysis of the 52 differentially regulated proteins demonstrated enrichment of proteins involved in complement activation, nitric oxide signaling, and with antioxidant activity. These enriched pathways may be suggestive of a persistent cardiomyopathy resulting from or predisposing to TTS.

Early-onset ST-segment elevation myocardial infarction (STEMI) in individuals under 50 is an increasing concern. Identifying new biomarkers could improve early diagnosis and intervention. In this case-control study, we investigated endothelial-related long non-coding RNAs (lncRNAs) MANTIS, NORAD, RNCR3, and SENCR as potential diagnostic markers. Blood samples from 200 young STEMI patients and 200 age-matched controls were analyzed using real-time PCR to evaluate lncRNA expression. NORAD and MANTIS levels were significantly reduced in STEMI patients (p < 0.001). MANTIS displayed the strongest association (AUC = 0.92), while NORAD demonstrated a moderate association (AUC = 0.68). SENCR and RNCR3 showed no significant differences between groups. The downregulation of MANTIS and NORAD suggests their potential roles as biomarkers in early-onset STEMI. MANTIS, in particular, may enhance risk stratification and treatment. Further research is warranted to validate these findings in broader populations.

Mitral regurgitation (MR) is a significant risk factor for heart failure, yet existing rodent models face limitations in invasiveness and reproducibility. This study established a novel percutaneous, ultrasound-guided rat model of MR to overcome these constraints. Thirty male Sprague-Dawley rats underwent echocardiography-guided mitral valve injury, allocated to severe MR (40-70% regurgitation), massive MR (> 70%), or sham groups. Serial echocardiographic assessments were performed at baseline, 30 min, and 2, 4, and 8 weeks post-procedure, with histological validation of myocardial fibrosis. The technique achieved 100% success with no acute mortality and enabled precise titration of regurgitation severity. Both MR groups exhibited progressive, body size-independent cardiac remodeling. Speckle-tracking revealed basal-segment-predominant longitudinal strain reduction, correlating with histologically confirmed peri-annular fibrosis. Survival was significantly lower in massive MR (40% vs. 90%, p = 0.006). This minimally invasive model reliably replicates human MR pathophysiology with high reproducibility and precise severity control, providing a robust platform for mechanistic investigation.

Myocardial ischemia-reperfusion injury (MIRI) involves tissue damage following restoration of blood flow. Stearoyl-CoA desaturase 1 (SCD1), associated with metabolic disorders, may contribute to MIRI. This study investigated the mechanism of SCD1 in MIRI. A rat ischemia/reperfusion (I/R) model was established by ligating the left anterior descending coronary artery. The hypoxia/reoxygenation (H/R) model was used to simulate in vitro I/R. 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry were performed for histopathological analysis of rat heart tissues. The ferroptosis indicators were detected using commercial kits and Western blot. Lactylation and ubiquitination of SCD1 were detected by Western blot. I/R increased tissue damage and SCD1 expression. In addition, SCD1 inhibition attenuated ferroptosis in H/R cells and I/R hearts. H/R induced ferroptosis via promoting lactylation modification in H9c2 cells. Mechanistically, lactylation of SCD1 at K208 stabilized its protein stability and activated Wnt/β-Catenin signaling to promote ferroptosis in H9c2 cells. In vivo, SCD1 silencing inhibited the MIRI. SCD1 lactylation drove ferroptosis in MIRI by regulating Wnt/β-Catenin signaling, offering potential therapeutic insights.

Glucagon-like peptide-1 (GLP-1) is a hormone mainly produced by intestinal L cells after meal, and its main functions include enhancing glucose-dependent insulin secretion, promoting insulin biosynthesis, inhibiting glucagon secretion, inhibiting gastrointestinal activity and regulating appetite. In recent years, GLP-1, besides its well-known hypoglycemic effects, has been shown to have beneficial effects in the cardiovascular field, but the precise molecular mechanism is not yet fully understood. GLP-1 receptor (GLP-1R) is a class B G-protein-coupled receptor (GPCR), which is widely distributed in the cardiovascular system. This review aims to summarize the GLP-1R dependent signaling pathways in GLP-1 cardiovascular protection and related researches, such as the GLP-1R structure, distribution and expression. Moreover, we also discussed the development of GLP-1R agonist (GLP-1RA) therapies in cardiovascular field.

The development of blood-wetted artificial organs is limited by thrombosis on synthetic biomaterial surfaces. In contrast, the endothelium of the vasculature creates a natural barrier to both thrombosis and pannus growth. Consequently, efforts have been made to endothelialize synthetic biomaterials used in blood-wetted devices. Therefore, this study was undertaken to provide a numerical model to simulate the inhibitory effects of EC-derived nitric oxide (NO) on platelet deposition. An existing multi-constituent continuum model of thrombosis was amended to incorporate shear-dependent generation of NO as an anticoagulant. A simulation was performed of blood flow through a bipartite parallel plate channel having an endothelialized upstream layer followed by a pro-coagulant collagen surface downstream. The simulation showed that endothelial-derived NO inhibited downstream platelet deposition, reducing thrombus growth and creating a thrombus-free zone immediately downstream. This enhanced simulation model of thrombosis provides insights into factors that may guide future endothelialization of artificial organs and other blood-wetted devices.