Cardiology Research Analysis

Integrated single-cell and spatial transcriptomics in infarcted human and mouse hearts identified a CD248-high fibroblast subset that stabilizes TGFβRI and induces ACKR3 to retain T cells, sustaining maladaptive fibrosis. Fibroblast-specific Cd248 deletion and interventional blockade with antibodies or engineered T cells reduced T-cell infiltration, scar expansion, fibrosis, and functional decline in preclinical models.

Impact: Defines a tractable stromal checkpoint linking fibroblast activation to adaptive immunity with interventional validation, nominating CD248 as a precision target to limit post-MI fibrosis.

Clinical Implications: Supports development of CD248-targeted antibodies or cell therapies to attenuate maladaptive scar expansion after MI and motivates biomarker strategies to identify CD248hi activity for patient selection.

Genome analysis of 11,555 congenital heart disease probands identified 60 dominant genes explaining ~10.1% of cases, with comparable contributions from de novo and transmitted variants and incomplete penetrance. Subtype and tissue specificity were mapped (e.g., NOTCH1 EGF-like cysteine-altering missense variants enriched in conotruncal defects), and brain-expressed genes were linked to neurodevelopmental delay.

Impact: Largest, well-powered mapping of dominant CHD genes with subtype specificity, directly informing diagnostic panels, counseling, and mechanistic stratification for precision care.

Clinical Implications: Supports expanded trio sequencing and refined, subtype-specific diagnostic panels; informs penetrance estimates for counseling and surveillance for extracardiac comorbidities.

Erythrocyte-derived extracellular vesicles (RBC-EVs) from type 2 diabetes patients are preferentially taken up by endothelial cells and transfer arginase-1, increasing oxidative stress and impairing endothelium-dependent relaxation. Inhibition of arginase—either EV cargo or vascular—or attenuation of oxidative stress mitigated dysfunction, nominating an EV→arginase-1 pathway as a targetable mechanism for diabetic endothelial injury.

Impact: Provides a concrete, targetable mechanistic link between circulating erythrocytes and endothelial dysfunction in diabetes, advancing beyond association to an intervenable pathway.

Clinical Implications: Arginase inhibition or strategies to reduce RBC-EV uptake could be explored as adjunctive therapies to improve endothelial function in T2D; RBC-EV arginase-1 burden may serve as a vascular risk biomarker.

Using human transcriptomics and myeloid-specific in vivo gain/loss models, HM13/SPP was identified as a driver of oxLDL-induced macrophage lipid loading via ER-associated degradation of HO-1. Myeloid HM13 overexpression accelerated foam cell formation and atherogenesis, while knockout was protective, nominating HM13/SPP inhibition and HO-1 stabilization as therapeutic strategies.

Impact: Reveals a previously unrecognized ERAD–HO-1 axis in foam cell biology and atherogenesis, offering a druggable intracellular node with multi-model validation.

Clinical Implications: Development of HM13/SPP inhibitors or HO-1 stabilizers could reduce foam cell burden and slow atherosclerotic progression; translational work on selectivity and safety is warranted.

In the phase 3, double-blind ATTRibute-CM RCT (n≈611, 30 months), acoramidis reduced the composite of all-cause mortality or first cardiovascular hospitalization (HR 0.64; 35.9% vs 50.5%) and reduced first CV hospitalization alone (HR 0.60), with early curve separation by month 3 and sustained benefit.

Impact: Provides definitive phase 3 evidence for a disease-modifying TTR stabilizer reducing mortality/CV hospitalization in ATTR-CM, directly changing standards of care.

Clinical Implications: Supports routine consideration of acoramidis for eligible ATTR-CM patients with standard amyloidosis monitoring protocols to reduce early and sustained risk.