In this study, we utilized the Olink Cardiovascular III panel to compare the expression levels of 92 cardiovascular-related proteins between patients with dilated cardiomyopathy combined with heart failure (DCM-HF) (n = 20) and healthy normal people (Normal) (n = 18). The top five most significant proteins, including SPP1, IGFBP7, F11R, CHI3L1, and Plaur, were selected by Olink proteomics. These proteins were further validated using ELISA in plasma samples collected from an additional cohort. ELISA validation confirmed significant increases in SPP1, IGFBP7, F11R, CHI3L1, and Plaur in DCM-HF patients compared to healthy controls. GO and KEGG analysis indicated that NT-pro BNP, SPP1, IGFBP7, F11R, CHI3L1, Plaur, BLM hydrolase, CSTB, Gal-4, CCL15, CDH5, SR-PSOX, and CCL2 were associated with DCM-HF. Correlation analysis revealed that these 13 differentially expressed proteins have strong correlations with clinical indicators such as LVEF and NT-pro BNP, etc. Additionally, in the GEO-DCM data sets, the combined diagnostic value of these five core proteins AUC values of 0.959, 0.773, and 0.803, respectively indicating the predictive value of the five core proteins for DCM-HF. Our findings suggest that these proteins may be useful biomarkers for the diagnosis and prediction of DCM-HF, and further research is prompted to explore their potential as therapeutic targets.

Purpose: Dilated cardiomyopathy (DCM) is a prevalent form of heart failure with limited therapeutic options. This study explores a novel treatment strategy involving the delivery of exosome-derived miRNA-185-5p inhibitors encapsulated in liposomes, aiming to target cardiac tissue and alleviate myocardial apoptosis and cuproptosis in DCM. Methods: The miRNA-185-5p inhibitor, identified in our previous study and extracted from exosomes, was encapsulated in liposomes functionalized with a cardiac-targeting peptide. This system was used in both in vitro and in vivo models of DCM induced by doxorubicin (DOX). We evaluated the effects of this treatment on cardiac function, apoptosis, cuproptosis, oxidative stress, and fibrosis using echocardiography, histological analysis, Western blotting, and biochemical assays. Results: In vitro experiments demonstrated that the Lipo@miR-185-5p inhibitor markedly attenuated apoptosis and cuproptosis in H9C2 cells and iPSC-derived cardiomyocytes, with a 42.6% reduction in apoptotic cell rates and over 50% downregulation of cuproptosis-related markers (both P < 0.01). In vivo, the targeted liposomal formulation significantly improved cardiac function in DOX-induced DCM mice, as evidenced by a 27.3% increase in left ventricular ejection fraction (LVEF) and a 36.5% reduction in myocardial fibrosis area (P < 0.01), along with enhanced survival. These findings underscore the therapeutic potential of this targeted delivery strategy for the treatment of dilated cardiomyopathy. Conclusion: Lipo@miR-185-5p inhibitor, utilizing exosome-derived miRNA and targeted liposomal delivery, effectively alleviates DCM-induced myocardial dysfunction. This approach represents a promising therapeutic strategy for cardiovascular diseases by targeting specific molecular mechanisms involved in heart failure.

Dilated cardiomyopathy (DCM), a form of non‐ischaemic myocardial disease, is characterised by structural and functional cardiac abnormalities. As defined by the World Health Organisation, DCM constitutes a significant cardiac pathology, leading to increased morbidity and mortality due to complications such as heart failure and arrhythmias. The diagnostic process for DCM predominantly employs echocardiography and MRI, with biomarkers like NT‐pro BNP and troponin providing supportive, yet non‐specific, evidence. Exosomes, small extracellular vesicles, play a critical role in intercellular communications by transferring biomolecules including lipids, proteins, messenger RNA (mRNA) and non‐coding RNA (ncRNA) to target cells, thereby influencing key cellular processes such as proliferation, differentiation, apoptosis, angiogenesis and immune modulation. Within the ncRNA category, circular RNAs (circRNAs) are notable for their cellular specificity and evolutionary conservation and are often implicated in the regulatory mechanisms underlying DCM and heart failure. This investigation employed next‐generation sequencing technology to analyse plasma exosomal circRNA profiles in DCM patients with chronic heart failure (CHF), compared to healthy controls. The analysis revealed distinct circRNA expression patterns, identifying 49 uniquely expressed circRNAs in the DCM cohort with CHF. These circRNAs were associated with several critical biological pathways, including the sequestration of extracellular ligands from receptors, N‐acetyltransferase activity, histone acetyltransferase activity and endocytic vesicle membrane composition. The findings of this study provide valuable insights into the pathophysiological mechanisms of DCM and offer evidence for improving clinical diagnostic methodologies.

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases with no effective treatment due to its complex pathogenesis. A novel cell death, disulfidptosis, has been extensively studied in the cancer field but rarely in cardiovascular diseases. This study revealed the potential relationship between disulfidptosis and hypertrophic cardiomyopathy and put forward a predictive model containing disulfidptosis-associated genes (DRGs) of GYS1, MYH10, PDMIL1, SLC3A2, CAPZB, showing excellent performance by SVM machine learning model. The results were further validated by western blot, RNA sequencing and immunohistochemistry in a TAC mice model. In addition, resveratrol was selected as a therapeutic drug targeting core genes using the CTD database. In summary, this study provides new perspectives for exploring disulfidptosis-related biomarkers and potential therapeutic targets for hypertrophic cardiomyopathy.