Aortic dissection (AD) is a highly lethal vascular disease characterized by separation of the constituent layers of the aortic wall. An increasing body of research indicates that inflammatory response and oxidative stress are implicated in vascular remodeling, which plays a key role in the development of AD. Hydrogen sulfide (H₂S) has been found to protect against various types of cardiovascular disease, including myocardial infarction, arthrosclerosis, and hypertension. However, research on the effect of H₂S on AD is insufficient. This study therefore elucidated the effect of H₂S on the development and progression of AD, and the potential mechanism involved. Using β-aminopropionitrile fumarate (BAPN) and angiotensin II (Ang-II)-induced AD animal models, the administration of NaHS (as H₂S donor, 56 μmol/kg body weight/day) was found to retard the development of AD. Murine VSMCs (Movas) exposed to interleukin-6 (IL-6) (20 ng/mL) to induce phenotypic switch. Histological analyses indicated that H₂S administration inhibited the accumulation of inflammatory cells in the aortic wall and the related expression of inflammatory genes. Additionally, H₂S treatment elevated aortic superoxide dismutase (SOD) activity and ablated malonaldehyde (MDA) and nitric oxide (NO) levels. In mechanistic terms, H₂S attenuated IL-6 induced a pathological VSMC phenotypical switch through NO modulation by N(G)-monomethyl-L-arginine acetate salt (L-NMMA) stimulation. H₂S inhibits AD formation by decreasing the inflammatory response, and oxidative stress, and by positively participating in vascular remodeling. These findings suggest a role for H₂S as a novel and promising therapeutic strategy to prevent AD development.

Myocardial infarction (MI) is a multifactorial global disease, recognized as one of the leading causes of cardiovascular morbidity and mortality. Timely and correct diagnoses and effective treatments could significantly reduce incidence of complications and improve patient prognoses. In this study, seven unconventional differentially expressed genes (DEGs) (MAN2A2, TNFRSF12A, SPP1, CSNK1D, PLAUR, PFKFB3, and CXCL16, collectively termed the MTSCPPC signature) were identified through integrating DEGs from six MI microarray datasets. The pathological and theranostic roles of the MTSCPPC signature in MI were subsequently analyzed. We evaluated interactions of the MTSCPPC signature with ovatodiolide, a bioactive compound isolated from Anisomeles indica (L.) Kuntze, using in silico molecular docking tools and compared it to specific inhibitors of the members of the MTSCPPC signature. Single-cell transcriptomic analysis of the public databases revealed high expression levels of the MTSCPPC signature in immune cells of adult human hearts during an MI event. The MTSCPPC signature was significantly associated with the cytokine–cytokine receptor interactions, chemokine signaling, immune and inflammatory responses, and metabolic dysregulation in MI. Analysis of a micro (mi)RNA regulatory network of the MTSCPPC signature suggested post-transcriptional activation and the roles of miRNAs in the pathology of MI. Our molecular docking analysis suggested a higher potential for ovatodiolide to target MAN2A2, CSNK1D, and TNFRSF12A. Collectively, the results derived from the present study further advance our understanding of the complex regulatory mechanisms of MI and provide a potential MI theranostic signature with ovatodiolide as a therapeutic candidate.

Aortic dissection (AD) is a life‑threatening vascular disorder with high mortality and no effective pharmacological treatment. Addressing its multicellular and dynamic pathology requires strategies that precisely modulate inflammatory and degenerative processes, yet existing targeted delivery approaches lack the spatiotemporal and cellular precision required. Here, we establish Galectin‑3 (Gal‑3) as a therapeutic delivery target for cardiovascular nanomedicine and introduce a modular, pathology‑tailored nanoplatform synergizing nitric oxide (NO) therapy with multi‑pathway intervention. Gal‑3 is persistently expressed on inflamed endothelial cells, macrophages, and smooth muscle cells during AD progression, providing a tractable target for lesion‑specific engagement. The nanoparticles, created from a previously unexplored integration of a Gal‑3‑binding polysaccharide, a nitric oxide–generating peptide, and a hydrophobic drug carrier, uniquely combine triple responsiveness to pH, protease, and oxidative stress with on‑demand NO release and controlled resveratrol co‑delivery. In vitro, they enhanced uptake across pathological cell types and attenuated inflammatory and degenerative phenotypes. In vivo, they achieved early lesion targeting, > 20‑fold aortic accumulation, and marked reductions in AD incidence, vascular degeneration, and mortality. This work establishes Gal‑3‑targeted nanotherapy as a broadly applicable paradigm for pathology‑adaptive intervention in AD and one that may be adapted for broader cardiovascular applications. Graphical Abstract

Spatiotemporal mapping of thrombus remodeling remains a major unmet challenge due to the lack of diagnostic tools capable of dynamically converting local biochemical activity into quantitative imaging signals. Current clinical methods lack sensitivity and specificity for accurate thrombus staging. Here, we present a programmable MRI nanoplatform enabling enzyme-gated dual-mode contrast switching for dynamic thrombus profiling and guided thrombolysis. The nanoprobe achieves broad-spectrum thrombus targeting by recognizing two complementary biomarkers uniquely expressed at distinct thrombus maturation stages, and integrates gelatin-guided structural reconfiguration with magnetic nanoparticle clustering to modulate MRI contrast. Gelatin modulates the nanoprobe structure, restricting water proton accessibility and promoting internal densification, thereby synchronously suppressing T1-weighted signals and amplifying T2-weighted contrast. Upon activation by thrombus-associated MMP-2/9, the nanoprobe disassembles, reversing its nano-architecture and signal behavior. This smart signal transformation quantitatively correlates with MMP activity, thrombus age, and collagen content, generating stage-dependent T1/T2 ratios. The nanoprobe also enables enzyme-triggered fibrinolytic release, achieving site-specific thrombolysis with minimal hemorrhagic risk. This materials-based strategy translates dynamic microenvironmental remodeling into high-resolution MRI outputs, establishing a programmable framework for precision imaging and therapy. These programmable imaging outputs support data-driven diagnostics, enable clinical treatment stratification, and offer a standardized reference for modeling enzyme-rich pathological environments. Graphical Abstract

Aortic dissection (AD) is a life-threatening vascular condition with limited pharmacological options, and shared risk factors with cardiac disease include hypertension, atherosclerosis, smoking, and dyslipidemia. This study investigated Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, in a BAPN/Ang-II-induced mouse model of AD, revealing significant therapeutic potential. Fer-1 significantly reduced AD incidence and mortality by preserving aortic wall integrity. RNA sequencing identified 922 differentially expressed genes, with 416 upregulated and 506 downregulated. Bioinformatics analysis revealed that Fer-1 modulates key regulators, such as MEF2C and KDM5A, impacting immune responses, oxidative stress, apoptosis, and lipid metabolism. Additionally, Fer-1 alters miRNA expression, with the upregulation of miR-361-5p and downregulation of miR-3151-5p, targeting pathways involved in inflammation, oxidative stress, and smooth muscle cell (SMC) phenotypic stability. Functional pathway analysis highlighted the inhibition of actin cytoskeleton, ILK, and IL-17 signaling, essential for SMC differentiation and extracellular matrix remodeling. Gene interaction network analysis identified 21 central molecules, including CXCR3, ACACA, and BPGM, associated with lipid metabolism, inflammation, and vascular remodeling. This research elucidates the mechanism of ferroptosis in AD pathogenesis and establishes Fer-1 as a promising therapeutic intervention. AD and cardiac diseases share molecular mechanisms, risk factors, and pathological processes, positioning AD within the broader scope of cardiovascular pathology. By attenuating lipid peroxidation, oxidative stress, and inflammation, Fer-1 may have cardioprotective effects beyond AD, providing a foundation for future translational research in cardiovascular medicine.