Journal of Cardiovascular Translational Research最新文献

Intraosseous access, the fastest access in emergencies, is exclusively used for delivering medications or fluids. The correlation between intraosseous and arterial pressures remains unclear. This study aimed to explore this correlation at baseline and in various clinical scenarios (e.g., different heart rates, arrhythmias, asystolic arrest, and CPR). In 11 male Yorkshire pigs (73.4 ± 5.9 kg), femoral artery and tibial Intraosseous lines were placed under anesthesia. Pressures were recorded during hemodynamic interventions and cardiac arrest. Analyses included Pearson's r, Wilcoxon rank-sum test, and BVAR. Intraosseous pressure showed correlating pulsatility with arterial pressure, ranging from 9 to 71% of mean arterial pressure. Correlation was strong under normal conditions (r = 0.75-0.96, p < 0.001) and during CPR (r = 0.65-0.99, p < 0.001), weakened during asystole (r = 0.26 ± 0.46, p < 0.001), and was disrupted by epinephrine (r = 0.04, p < 0.001). Asystole was identifiable on intraosseous tracings. Intraosseous pressure effectively reflects circulatory activity and may aid in accurately identifying asystole with possible clinical implications for CPR.

Exposure to cold environments is physiologically challenging, with extreme cold stress (ECS) impairing the function of the left ventricle (LV) of the heart. We aimed to determine the role and mechanism of action of the miR-499-5p/phosphofurin acidic cluster sorting protein 2 (PACS2)/transient receptor potential cation channel subfamily V member 1 (TRPV1) axis in ECS-induced cardiomyocyte injury and LV dysfunction. Mice were placed in a -20 °C chamber to simulate an extremely cold environment. MiR-499-5p overexpression in the mice decreased PACS2 levels, and mitochondrial function was inhibited in vivo following ECS. Inhibiting miR-499-5p enhanced PACS2 expression, thereby reversing the structural and functional LV deficits caused by ECS. Cardiac-specific Pacs2 knock-in restored the decreases in mitophagy and mitochondrial energy metabolism caused by ECS via enhancing endoplasmic reticulum-mitochondrial calcium flux through TRPV1, a nonselective calcium channel. The findings indicate targets for preventing cardiac disease during exposure to extremely cold environments.

Low preoperative heart rate variability (HRV) is associated with adverse cardiovascular outcomes and delirium after geriatric surgery, but in-person testing is burdensome and impractical. To evaluate wrist-based wearables for remotely capturing preoperative outpatient and postoperative inpatient data for HRV analysis. RR-intervals were extracted, and data missingness was assessed for systematic differences. Delirium incidence was evaluated. Preoperatively, 76.9% of participants provided high-quality outpatient data, with no systematic demographic or clinical differences. Postoperatively, 80.2% had high-quality inpatient data; however, missing data were associated with older age, lower BMI, ICU admission, and longer surgeries and hospitalizations. Postoperative HRV did not significantly differ between participants with and without delirium. Outpatient HRV capture via wrist-based wearables is broadly feasible in older surgical patients, while postoperative inpatient data are disproportionately missing in higher-risk patients. These differences highlight both the translational potential and limitations of wearable HRV measurements for perioperative outcome prediction.

For decades, the pathogenesis of Acute Rheumatic Fever and Rheumatic Heart Disease has been primarily attributed to autoimmune activation in genetically predisposed children, triggered by molecular mimicry between Group A Streptococcus antigens and cardiac tissue components. Recent evidence reveals that immune priming generates complement-fixing and non-complement-fixing cross-reactive antibodies, initiating inflammatory cascades. Tissue-infiltrating neutrophils, T lymphocytes, macrophages, and neutrophil extracellular traps (NETs) critically contribute to rheumatic carditis immunopathology. These effectors damage endothelium, release acute-phase reactants, facilitate infiltration, exposing autoantigens, and promoting epitope spreading. All the three complement pathways emerge as key inflammatory amplifiers enhancing NET formation (NETosis) via PAD4-mediated histone citrullination, depositing on NET scaffolds, stabilizing them and perpetuating tissue injury. Dysregulated complement-NET interactions drive progression from acute inflammation to chronic valvular fibrosis. Circulating biomarkers such as cell-free DNA, MPO-DNA complexes, and complement fragments may indicate disease activity. Emerging therapeutic strategies include PAD4 inhibition, DNase-based NET clearance, and complement modulation.

Device-based therapies may augment decongestion in acute decompensated heart failure. We investigated the efficacy and safety of prolonged mechanical superior vena cava occlusion using the preCARDIA system in a swine model of heart failure. Over 6 h of preCARDIA activation, right- and left-sided filling pressures were significantly reduced. Plasma levels of the brain injury marker ubiquitin C-terminal hydrolase L1 and intracerebral arterial pressure were not significantly changed. Post-mortem evaluation did not identify gross cerebral or histologic injury. Future studies are needed to compare continuous versus cyclic preCARDIA activation and to further confirm the neurologic safety of sustained superior vena cava occlusion.

Heart failure is the leading cause of hospitalization globally, burdening healthcare systems and the economy. Heart failure is a multifactorial cardiac syndrome, where the heart fails to maintain sufficient cardiac output to support body function. As the population ages, heart failure rates will increase. Current treatments, such as medications and surgery, are not suitable for all patients, creating a need for alternative therapies. Gene therapy offers promising new approaches, with therapeutic angiogenesis, regenerative strategies, and calcium ion regulation as key targets. SERCA2a plays a critical role in calcium regulation, and clinical trials have focused on its potential as a therapeutic agent. VEGF-B, which specifically targets the myocardium, also regulates myocardial metabolism and SERCA2a activity. Although clinical trials have been conducted, results have not consistently replicated pre-clinical success. This review summarizes the current state of gene therapy for heart failure, including therapeutic agents, vectors, delivery methods, and preclinical models.

This study explored the association between 19 peripheral artery disease (PAD)-associated variants and PAD severity. We classified PAD cases into 4 groups with increasing levels of severity based on age of PAD diagnosis and surgical status. Genetic association analysis for PAD severity and markers was conducted using REGENIE, and a 19-variant polygenic risk score (PRS) was developed to further evaluate the associations with severity subtypes. Two SNPs (rs4722172 and rs505922) showed stronger odds ratios (ORs) with more severe subtypes. The 19-variant PRS was significantly higher in surgical compared to non-surgical groups (OR = 1.14, 95% CI: 1.08, 1.20; p-value = 5.85 × 10^-7) while no significant difference for non-premature and premature PAD (OR = 0.98, 95% CI: 0.9, 1.07, p-value = 0.64). This same pattern was observed in the subjects from Generations dataset. Our findings demonstrate that PAD-associated SNPs may also be associated with PAD severity as assessed by surgical intervention and age of onset (or diagnosis).

Myocardial ischemia-reperfusion injury (MIRI) is an unresolved clinically fatal complication in the management of acute myocardial infarction (AMI). Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) plays a vital role in the regulation of MIRI. However, the underlying mechanisms remain unclear. GADD45G and SP1 expression were upregulated in hypoxia/reoxygenation (H/R)-treated H9C2 cells. H/R treatment repressed H9C2 cell viability, and induced apoptosis, oxidative stress, and inflammatory response. Moreover, GADD45G deficiency could relieve H/R-triggered H9C2 cell injury. In mechanism, SP1 was a transcription factor of GADD45G and activated the transcription of GADD45G via binding to its promoter region. Besides, SP1 knockdown alleviated MI/R-induced pathological damage in the myocardial tissue of rats by regulating GADD45G. In conclusion, SP1 could promote H/R-induced cardiomyocyte injury and MI/R-caused rat myocardial tissue pathological injury by increasing GADD45G, providing a promising therapeutic target for MIRI treatment.

Ischemic mitral regurgitation (IMR) commonly complicates pPCI in STEMI patients. GDF11, a protective cardiovascular factor, may influence IMR progression and prognosis. Among 310 STEMI patients, 126 with recent normal echocardiography underwent pPCI with pre-procedural GDF11 testing. Cox regression, ROC analysis, and Spearman's correlation assessed GDF11's predictive value for IMR exacerbation and cardiac function. Lower GDF11 predicted IMR worsening (HR = 0.982, P = 0.004; AUC = 0.744, P < 0.001). High GDF11 patients had reduced IMR progression (P = 0.0013) and heart failure risk (P = 0.0003). GDF11 correlated with LVEF and left atrial changes (P < 0.05). Serum GDF11 independently predicts IMR exacerbation and post-pPCI heart failure, serving as a prognostic biomarker in STEMI.

Testosterone (TES) has complex roles in cardiovascular disease, influencing not only atherosclerosis development in general, but also atherosclerosis-related processes associated with hypertension, cholesterol metabolism, vascular calcification, and arterial stiffness. This review examines TES's effects, particularly its atheroprotective role in various mice and minipig model systems and cell cultures. TES modulates the renin-angiotensin system (RAS), contributing to hypertension and vascular dysfunction, but its deprivation can mitigate these effects. TES also impacts cholesterol metabolism by regulating liver X receptor (LXRα) pathways, promoting both cholesterol clearance and synthesis. Moreover, TES is involved in vascular calcification via androgen receptor (AR) signalling, a process that contributes to arterial stiffness, especially in females. The review highlights gaps in understanding TES's specific molecular mechanisms in cardiovascular disease, emphasising the need for further research to explore sex-specific responses and potential therapeutic interventions.