Hybrid intravascular ultrasound-optical coherence tomography (IVUS-OCT) can enable more accurate plaque characterization than single-modality intravascular imaging, enhancing treatment planning and vulnerable plaque detection. However, image interpretation in IVUS-OCT is challenging and time-consuming. To overcome this limitation, we introduce a novel histology-trained deep learning (DL)-classifier for plaque component classification in IVUS-OCT images and compare its performance against single-modality DL and expert analysts. IVUS-OCT frames and matched histological sections from 10 cadaveric human hearts were included in this analysis. The histological data were used to define fibrotic, calcific, and necrotic core tissue regions of interest (ROIs) in IVUS-OCT and used to train three DL-classifiers for IVUS, OCT, or hybrid IVUS-OCT image analysis (992 frames) and test their performance (264 frames). The test set was additionally annotated by experts from three different core labs, and their estimations and those of the DL-classifiers were compared with histology.The IVUS-OCT DL-classifier had a superior performance to the IVUS-DL, OCT-DL, and the expert analysts in detecting plaque phenotypes (Kappa 0.60 vs. 0.19, 0.35, and 0.53, respectively) and accurately classified 68% of histologically defined fibroatheromas. The hybrid IVUS-OCT DL-classifier also had a better performance than single-modality DL-classifiers and the experts in assessing tissue types in ROIs annotated by histology (overall accuracy 86.7% compared with 73.2% for IVUS-DL, 66.6% for OCT-DL, and 70.6% for the experts). Plaque characterization using a histology-trained hybrid IVUS-OCT DL-classifier is feasible and enables more accurate detection of plaque components and phenotype classification than single-modality DL-classifiers and expert analysts.

The burden of dyslipidaemia is increasing, and the association of dietary exposure, especially vegetable consumption, with dyslipidaemia among Africans is poorly characterized. This study evaluated the relationship between vegetable consumption and dyslipidaemia among Africans. The frequency of vegetable consumption (servings/week) was assessed in this study involving 13 172 participants, including 6586 pairs of dyslipidaemia cases and non-cases (matched for age within ±5 years, sex, and country), in a matched case-control design. Multivariable-adjusted conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the odds of dyslipidaemia across quartiles of frequency of vegetable consumption at a two-sided P < 0.05. The mean age was 52.18 ± 10.15 years, and 6898 (52.4%) were females. The median (IQR) vegetable consumption intake was 7.0 (2.0, 14.0) servings per week and the prevalence of dyslipidaemia by the distribution of vegetable consumption was 1776 (52.0%) for low (first quartile), 1530 (49.9%) for moderate (second quartile), 1720 (49.2%) for sufficient (third quartile), and 1560 (48.9%) for high (fourth quartile) frequency of vegetable consumption. The multivariable-adjusted OR (95%CI) of dyslipidaemia odds by the distribution of vegetable consumption were 1.00 for low, 0.89 (0.80, 0.99) for moderate, 0.84 (0.75, 0.93) for sufficient, and 0.81 (0.72, 0.92) for high; P for trend = 0.005, with a OR (95%CI) of 0.97 (0.94, 0.99) per +7 servings/week change after adjusting for age, family history of cardiovascular diseases, education, ever smoked, currently consume alcohol, physical inactivity, body mass index, diabetes mellitus status, and hypertension. A similar trend was observed for low high-density lipoprotein (<40 mg/dL): 1.00 for low, 0.90 (0.78, 1.04) for moderate, 0.93 (0.81, 1.06) for medium, and 0.80 (0.68, 0.94) for high; P for trend = 0.01, adjusting for similar covariates. Higher vegetable consumption was associated with lower odds of dyslipidaemia in this sample of Africans after accounting for multiple covariates.

Sodium-glucose co-transporter 2 inhibitors are widely used to treat patients with type 2 diabetes and exhibit beneficial cardiovascular effects beyond glucose lowering. In this study, we investigated their potential to alleviate vaso-occlusive events and organ damage in sickle cell disease (SCD) mice. Intravital and immunofluorescence microscopy reveal that a 4-day oral administration of dapagliflozin (DAPA) or sotagliflozin (SOTA) significantly reduces neutrophil adhesion and transmigration in cremaster venules, with SOTA showing greater inhibition, and down-regulates E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in cremaster venules of TNF-α-challenged SCD mice. Intriguingly, only SOTA improves mouse survival acutely. Similar inhibitory effects on neutrophil recruitment are observed in SCD mice subjected to hypoxia-reoxygenation. Flow chamber assays indicate that neither drug directly affects neutrophil or endothelial cell adhesive function. In addition, treatment of neutrophils and platelets from SCD mice and patients with DAPA or SOTA does not affect their activation. When administered for 4 months, DAPA or SOTA mitigates neutrophil recruitment and enhances microcirculation in cremaster venules of TNF-α-challenged SCD mice, while only SOTA confers a survival benefit. Both drugs reduce leucocyte infiltration in the liver or lungs, suggesting their ability to protect against organ damage. Co-administration with hydroxyurea for 4 months does not enhance these effects. Multiplex analysis shows that DAPA and SOTA lower plasma levels of soluble P-selectin, ICAM-1, S100A8/A9, and pro-inflammatory cytokines in SCD mice. Our findings suggest that DAPA and SOTA mitigate vaso-occlusive events in SCD, with SOTA providing superior benefits.

Mammalian cardiac development and homeostasis rely on tightly coordinated transcriptional programs driven by core cardiogenic transcription factors. Among these, GATA binding protein 4 (GATA4) plays a pivotal role-not only in orchestrating embryonic heart formation, but also in modulating cardiac adaptation to physiological and pathological stress. To fulfil its canonical functions, emerging evidence reveals that GATA4 activity is shaped by a multilayered regulatory network involving chromatin dynamics, transcriptional and post-transcriptional inputs, and diverse post-translational modifications. In this review, we provide an integrated overview of the roles of GATA4 across developmental stages, postnatal physiology, and disease contexts. We further examine how chromatin occupancy and regulatory mechanisms fine-tune GATA4 function and evaluate current strategies that leverage GATA4 modulation for cardiac repair and regeneration. By highlighting both established and underexplored facets of GATA4 biology, this review establishes GATA4 as a central regulator of cardiac identity and plasticity, with broad implications for developmental biology, cardiac physiology, and therapeutic innovation.

The Rho kinases 1 and 2 (ROCK1/2) are serine-threonine specific protein kinases that control actin cytoskeleton dynamics. They are expressed in all cells throughout the body, including cardiomyocytes, smooth muscle cells and endothelial cells (ECs), and are intimately involved in cardiovascular health and disease. Pharmacological ROCK inhibition is beneficial in mouse models of hypertension, atherosclerosis, and neointimal thickening that display overactivated ROCK. However, the consequences of endothelial ROCK signalling deficiency in vivo remained unknown. To address this issue, we generated Cdh5CreERT2 driven, tamoxifen inducible loss of function alleles of ROCK1 and ROCK2 and analysed mouse survival and vascular defects through cellular, biochemical, and molecular biology approaches. We observed that postnatal or adult loss of endothelial ROCK1 and 2 was lethal within a week. Mice developed multi-organ haemorrhage along with loss of vascular integrity. ECs displayed deficient cytoskeletal actin polymerization that prevented focal adhesion formation and disrupted junctional integrity. Retinal sprouting angiogenesis was also perturbed, as sprouting vessels exhibited lack of polymerized actin and defective lumen formation. In a three-dimensional endothelial sprouting assay, combined knockdown of ROCK1/2 or individual knockdown of ROCK2 but not ROCK1 led to reduced sprouting, lumenization and cell polarization defects caused by defective actin and altered VE-cadherin dynamics. The isoform specific role of endothelial ROCK2 correlated with ROCK2 substrate specificity for FAK and LIMK. By analysing single and three allele mutants we show that one intact allele of ROCK2 is sufficient to maintain vascular integrity in vivo. Endothelial ROCK1 and 2 maintain junctional integrity and ensure proper angiogenesis and lumen formation. The presence of one allele of ROCK2 is sufficient to maintain vascular growth and integrity. These data indicate the need for careful consideration when using ROCK inhibitors in disease settings.