Yong He

Coronary stent implantation remains a cornerstone therapy for coronary artery disease, yet current stent technologies continue to face limitations including acute and late thrombosis, delayed re-endothelialization, chronic inflammation, and in-stent restenosis. These complications largely arise from the nonphysiological interface between the implanted device and the injured vascular microenvironment. Biomembrane-camouflaged stents have recently emerged as a promising strategy to engineer biologically instructive blood-contacting surfaces by integrating natural or artificial membrane systems onto stent platforms. In this review, we summarize recent advances in three major biomembrane-based strategies for coronary stent functionalization: cell membrane-camouflaged stents, liposome-camouflaged stents, and exosome-camouflaged stents. Biomimetic cell membrane coatings retain native bioactive signals that collectively facilitate immune evasion, thromboresistance, and vascular healing. Liposome-based coatings are tunable artificial biomembrane reservoirs for the localized delivery of anticoagulants, anti-inflammatories, nitric oxide releasers, antiproliferatives, and gene therapies. Exosome-functionalized stents further enable bioactive intercellular communication by transferring endogenous regulatory cargos that modulate endothelial regeneration, macrophage polarization, smooth muscle cell phenotype, oxidative stress, and neointimal remodeling. We further discuss fabrication approaches, biological mechanisms, preclinical evidence, translational barriers, and future design principles for these platforms. Although challenges remain in coating durability, sterilization, long-term storage, manufacturing reproducibility, and clinical validation, biomembrane-camouflaged stents represent a compelling direction for next-generation coronary intervention by transforming conventional stents from passive mechanical scaffolds into active regulators of vascular repair.

Introduction The ‘strike early and strike strong’ lipid-lowering strategy emphasises rapid reduction of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are increasingly used alongside statins to achieve guideline-recommended LDL-C targets after ACS. However, despite substantial LDL-C reductions with early PCSK9i initiation, their effects on non-culprit coronary atherosclerotic plaques remain unclear. This study aims to assess the impact of early intensive LDL-C lowering with PCSK9i added to moderate-intensity statin therapy on optical coherence tomography (OCT)-derived plaque characteristics in non-culprit coronary lesions in patients with ACS. Methods and analysis In this prospective, multicentre, open-label trial, 212 patients with ACS will be randomised 1:1 to an early intensified lipid-lowering strategy (PCSK9i added to moderate-intensity statin) or guideline-directed medical therapy for 6 months. Serial OCT imaging of non-culprit coronary arteries with 20–70% stenosis will be performed at baseline and 6 months. The primary endpoint is the absolute change in minimum fibrous cap thickness within a matched target arterial segment from baseline to 6 months. Secondary endpoints include changes in minimum lumen area, maximum lipid arc, presence of macrophage infiltration, LDL-C reduction and achievement of LDL-C targets. The primary endpoint will be analysed using analysis of covariance, adjusting for treatment group, baseline LDL-C stratification (≥1.8 vs Ethics and dissemination Ethics approval was granted by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2024 Review No 1943). Results will be disseminated via peer-reviewed publications and presentations at academic conferences. Trial registration number NCT06791031.

Mitochondria-associated membranes (MAMs) are pivotal in cellular homeostasis, mediating communication between the endoplasmic reticulum and mitochondria. They are increasingly recognized for their role in atherosclerosis and coronary artery disease (CAD). This review delves into the cellular perspective of MAMs' impact on atherosclerosis and CAD, highlighting their influence on disease progression and the potential for therapeutic intervention. MAMs are implicated in key pathophysiological processes such as the generation of reactive oxygen species, calcium homeostasis, myocardial ischemia-reperfusion injury, autophagy, lipid synthesis and transport, and energy metabolism—fundamental to the development and progression of atherosclerosis and CAD. The complex interplay of MAMs with these pathological processes underscores their potential as therapeutic targets. This review synthesizes current understanding and emphasizes the need for further research to elucidate the multifaceted roles of MAMs in atherosclerosis and CAD, offering avenues for developing novel strategies aimed at improving mitochondrial health and mitigating the impact of these conditions.

Background: Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have recently emerged as critical mediators in cardiovascular pathophysiology; however, their specific contributions to CHD pathogenesis remain largely unexplored. Objective: This study aimed to identify and validate MAM-related biomarkers in CHD through integrated analysis of transcriptomic sequencing data and Mendelian randomization, and to elucidate their underlying mechanisms. Methods: We analyzed two gene expression microarray datasets (GSE113079 and GSE42148) and one genome-wide association study (GWAS) dataset (ukb-d-I9_CHD) to identify differentially expressed genes (DEGs) associated with CHD. MAM-related DEGs were filtered using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis, Mendelian randomization, and machine learning algorithms were employed to identify biomarkers with direct causal relationships to CHD. A diagnostic model was constructed to evaluate the clinical utility of the identified biomarkers. Additionally, we validated the two hub genes in peripheral blood samples from CHD patients and normal controls, as well as in aortic tissue samples from a low-density lipoprotein receptor-deficient (LDLR−/−) atherosclerosis mouse model. Results: We identified 4174 DEGs, from which 3326 MAM-related DEGs (DE-MRGs) were further filtered. Mendelian randomization analysis coupled with machine learning identified two biomarkers, DHX36 and GPR68, demonstrating direct causal relationships with CHD. These biomarkers exhibited excellent diagnostic performance with areas under the receiver operating characteristic (ROC) curve exceeding 0.9. A molecular interaction network was constructed to reveal the biological pathways and molecular mechanisms involving these biomarkers. Furthermore, validation using peripheral blood from CHD patients and aortic tissues from the Ldlr−/− atherosclerosis mouse model corroborated these findings. Conclusions: This study provides evidence supporting a mechanistic link between MAM dysfunction and CHD pathogenesis, identifying candidate biomarkers that have the potential to serve as diagnostic tools and therapeutic targets for CHD. While the validated biomarkers offer valuable insights into the molecular pathways underlying disease development, additional studies are needed to confirm their clinical relevance and therapeutic potential in larger, independent cohorts.

Background: Patients with acute coronary syndrome (ACS) face a significantly increased risk of cardiovascular events due to vulnerable plaques. However, no clear evidence supports performing preventive percutaneous coronary intervention (PCI) for non‐flow‐limiting vulnerable plaques. To address this gap, the PASSIVATE‐CAP study was designed to investigate the therapeutic potential of drug‐coated balloon (DCB) for treating non‐flow‐limiting vulnerable plaques. Methods: The PASSIVATE‐CAP study is an investigator‐initiated, prospective, randomized, multicenter, open‐label superiority trial focusing on acute coronary syndrome (ACS) patients with non‐flow‐limiting vulnerable plaques in non‐culprit vessels. In this study, eligible patients will be randomized at a 1:1 ratio into two groups: patients who received guideline‐directed medical therapy (GDMT) and patients who received GDMT combined with a drug‐coated balloon (DCB). The primary endpoint was the minimal lumen area of the target lesion 1 year after randomization. The secondary endpoints encompass a range of factors, including the proportion of patients with vulnerable plaques in the target vessel, fibrous cap thickness, lipid core arc of the target lesion, minimal lumen area of the target vessel, among others. The study has been registered on Clinicaltrials.gov (Identifier: NCT06416813). Results: The PASSIVATE‐CAP study enrolled its first patient on July 14, 2025, with projected enrollment completion by January 31, 2027. As of December 28, 2025, 6 patients have been enrolled. The anticipated study end date, marking the completion of the follow‐up period, is January 31, 2028. Conclusions: The PASSIVATE‐CAP study represents the first prospective, randomized, multicenter, open‐label trial designed to explore the therapeutic value of DCB for the treatment of vulnerable plaques within the ACS patient population.

Kawasaki disease (KD) may cause coronary aneurysms and calcified stenosis, posing challenges for percutaneous coronary intervention (PCI). The role of drug‐coated balloons (DCB) in this context remains uncertain. We report a 25‐year‐old man with prior KD who developed 90% calcified stenosis at the inlet of a left anterior descending artery aneurysm. Optical coherence tomography (OCT) confirmed severe calcification. Predilatation with a cutting balloon followed by paclitaxel‐coated balloon angioplasty achieved lumen enlargement without dissection. Six‐month angiography and OCT showed a patent vessel with smooth healing, and the patient remained event‐free during 4 years of follow‐up under antiplatelet and lipid‐lowering therapy. This case highlights that intravascular imaging‐guided, stent‐free PCI with DCB may offer a feasible revascularization approach for KD‐related calcified coronary stenosis, although long‐term efficacy requires further evaluation.