Journal of Cardiovascular Translational Research最新文献

Epidemiological studies have revealed that patients with higher levels of high-density lipoprotein cholesterol (HDL-C) were more resistant to cardiovascular diseases (CVD), and yet targeting HDL for CVD prevention, risk assessment, and pharmacological management has not proven to be very effective. The mechanistic investigations have demonstrated that HDL exerts anti-atherogenic functions via mediating reverse cholesterol transport, antioxidant action, anti-inflammatory activity, and anti-thrombotic activity. Contrary to expectations, however, adverse cardiovascular events were reported in clinical trials of drugs that raised HDL levels. This has sparked a debate between HDL quantity and quality. Patients with atherosclerotic CVD are associated with dysfunctional HDL, and the degree of HDL dysfunction is correlated with the severity of the disease, independent of HDL-C levels. This growing body of evidence has underscored the need for integrating HDL functional assays in clinical practice for CVD risk management. Because HDL exerts diverse athero-protective functions, there is no single method for capturing HDL functionality. This review critically evaluates the various techniques currently being used for monitoring HDL functionality and discusses key structural changes in HDL indicative of dysfunctional HDL and the technical challenges that need to be addressed to enable the integration of HDL function-based metrics in clinical practice for CVD risk estimation and the development of newer therapies targeting HDL function.

Right ventricular (RV) strain offers crucial diagnostic insights in cardiovascular and pulmonary disorders. Nonetheless, the absence of established reference values impedes its clinical implementation. Utilizing CMR-feature tracking, age- and gender-dependent RV strains were systematically assessed in 175 heart-healthy Caucasians, 97 females, median 32.5 years. RV global longitudinal strain (GLS) was greater in females than males (median -26.8% (-28.3;-24.1) vs. -24.4 ± 3.0%; p < 0.001), whereby radial and circumferential strain remained comparable. Age subgroups exhibited increased RV-GLS for group B (30–50 years) (-26.0 ± 3.1% vs. -24.4 ± 3.2%; p = 0.011) and group C (> 50 years) (-26.7 ± 2.3% vs. -24.4 ± 3.2%; p < 0.001) compared to group A (< 30 years). High intra-class correlation coefficients (ICC) were exhibited by intrarater variability (ICC = 0.86–0.95) and moderate levels for interrater variability (ICC = 0.50–0.73). CMR-feature tracking provides a fair quantification method of age- and gender-specific normal RV strain values, demonstrating that higher RV-GLS is linked to female gender and advancing age within a healthy Caucasian cohort.

Graphical Abstract

Right-ventricular global longitudinal strain, assessed by cardiac MRI feature-tracking, increases with the female sex and advancing age within a Caucasian cohort of healthy subjects (N = 175)

The Impella CP is a percutaneously inserted temporary left ventricular assist device used in clinical practice and in translational research into cardiogenic shock, perioperative cardiac surgery, acute cardiac failure and mechanical circulatory support. Fluoroscopic guidance is usually used for insertion of an Impella, thus limiting insertion to within catheterization laboratories. Transthoracic, transoesophageal and intracardiac echocardiography have been reported to guide Impella CP implantation with identified specific limitations stemming from the surgical, anatomical and equipment factors. We conducted translational prospective descriptive feasibility investigation as a part of two other hemodynamic Impella studies. It showed the successful application of epicardial echocardiographic scanning for implantation of Impella CP devices in ovine models, from which details of the technique and identified pitfalls are described with practical solutions for future investigators and clinicians. Many described findings are relevant to any other echocardiographic techniques when adequate imaging of the Impella and relevant anatomical structures is achievable.

Graphical Abstract

Absent in melanoma 2(AIM2) exacerbates atherosclerosis by inflammasome assembly. However, AIM2-mediated inflammation in diabetic cardiomyopathy remains incompletely understood. Here we investigate the role of AIM2 in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. By RNA-seq, we found that AIM2 were significantly upregulated in HG-induced macrophages, upregulation of AIM2 in cardiac infiltrating macrophages was confirmed in a high-fat diet (HFD)/streptozotocin (STZ)-induceddiabetic mouse model . Therefore, AIM2 knockout mice were constructed. Compared to WT mice, HFD/STZ-induced cardiac hypertrophy and dysfunction were significantly improved in AIM2^-/- mice, despite no changes in blood glucose and body weight. Further, AIM2 deficiency inhibited cardiac recruitment of M1-macrophages and cytokine production. Mechanistically, AIM2-deficient macrophgaes reduced IL-1β and TNF-α secretion, which impaired the NLRC4/IRF1 signaling in cardiomyocytes, and reduced further recruitment of macrophages, attenuated cardiac inflammation and hypertrophy, these effects were confirmed by silencing IRF1 in WT mice, and significantly reversed by overexpression of IRF1 in AIM2^-/- mice. Taken together, our findings suggest that AIM2 serves as a novel target for the treatment of diabetic cardiomyopathy.

Intrapericardial administration has been proposed as an alternative delivery route of pharmacological agents via the bilaminar sac of pericardium surrounding the heart. To date, intrapericardial administration has entailed the localized administration of a broad spectrum of therapeutic agents. These agents include stem cells, extracellular matrix, growth factor, drugs, bioactive materials, and genetic materials, to the heart and coronary arteries. The route not only overcomes the limitations associated with traditional systemic administration methods, but also presents multiple intrinsic advantages over the other approaches, allowing greater therapeutic actions. Intrapericardial administration exhibits versatility in addressing certain cardiac conditions and ongoing research in this field certainly holds promise for further innovations and advancements to improve cardiac treatment. Thus, this review discusses the anatomy and physiology of the pericardium, the intrapericardial administration access routes, the recent application of intrapericardial delivery in the context of cardiac repair as well as the challenges associated with the approach.

Hypertrophic cardiomyopathy is often caused by pathogenic MYBPC3 variants. The study of Italian patients with HCM and MYBPC3(NM_000256.3):c.913_914del showed a higher disease penetrance in males and a higher frequency of arrhythmias compared to patients with other likely pathogenic and pathogenic (LP/P) MYBPC3 variants. We investigated the clinical outcomes of Slovenian probands with MYBPC3 LP/P variants, estimated the variant penetrance and compared the results with an Italian study. We identified 31 haplotype-matched individuals with MYBPC3:c.913_914del and 34 individuals with other LP/P MYBPC3 variants. We observed some significant differences in clinical and echocardiographic characteristics and frequency of adverse cardiac events between Slovenian and Italian probands with MYBPC3:c913_914del. We were unable to replicate previous findings for MYBPC3:c.913_914del, highlighting the complexity of genotype-phenotype associations.

The study investigates the utility of heart fatty-acid binding protein (H-FABP) in distinguishing TIA from mimics. Data from 175 patients from the StrokeChip multicenter study was retrospectively analyzed. H-FABP level was measured using a rapid point-of-care test. Findings revealed that H-FABP levels were higher in individuals with TIA compared to mimics [3.10 ng/mL (IQR 2.13-4.78) vs. 1.70 ng/mL (IQR 1.23-2.38)] (p < 0.001). The diagnostic performance of H-FABP, assessed using the area under the curve operating characteristic curve (AUC) was 0. 83 (95% CI = 0.76-0.90) for the final model, indicating good discriminative ability. The PanelomiX determined that a combined cutoff of > 1.85 ng/ml for H-FABP, age > 42.5 years, and baseline NIHSS > 3.5 had a 100% of sensitivity and 23.30% of specificity. The study suggests that H-FABP has potential as a TIA diagnostic biomarker. The rapid application of POCT's for H-FABP measurement supports its potential use in emergency departments and primary care settings.

The objective of this preclinical study was to evaluate the feasibility and safety of transcatheter endocardial alginate hydrogel injection (TEAi) in a large animal model, utilizing the high-stiffness XDROP® alginate hydrogel in combination with the dedicated EndoWings® catheter-based system. All swine (n = 9) successfully underwent TEAi without complications. Acute results from a subset of animals (n = 5) demonstrated the ability of the catheter to access a wide range of endomyocardial areas and achieve consecutive circumferential hydrogel distribution patterns within the mid-left ventricular wall. Histological examinations at 6 months (n = 4) demonstrated that the XDROP® remained localized within the cardiac tissue. In addition, serial echocardiographic imaging showed that XDROP® had no adverse impacts on LV systolic and diastolic functions. In conclusion, this innovative combination technology has the potential to overcome the translational barriers related to alginate hydrogel delivery to the myocardium.

Rehabilitation exercise is a crucial non-pharmacological intervention for the secondary prevention and treatment of cardiovascular diseases, effectively ameliorating cardiac remodeling in patients. Exercise training can mitigate cardiomyocyte apoptosis, reduce extracellular matrix deposition and fibrosis, promote angiogenesis, and regulate inflammatory response to improve cardiac remodeling. This article presents a comprehensive review of recent research progress, summarizing the pivotal role and underlying mechanism of rehabilitation exercise in improving cardiac remodeling and providing valuable insights for devising effective rehabilitation treatment programs. Graphical Abstract.