The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti‐aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2‐mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE ^−/− mice on a high‐fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.

Coronary artery bypass grafting (CABG) is the gold standard procedure for multi vessels and left main coronary artery disease. The prognosis and survival outcomes of CABG surgery are highly dependent on the patency of the bypass graft. Early graft failure which can occur during or soon after CABG remains a significant issue, with reported incidences of 3–10%. Graft failure can lead to refractory angina, myocardial ischemia, arrhythmias, low cardiac output, and fatal cardiac failure, emphasizing the importance of ensuring graft patency during and after surgery to prevent such complications. Technical errors during anastomosis are among the leading causes of early graft failure. To address this issue, various modalities and techniques have been developed to evaluate graft patency during and after CABG surgery. These modalities aim to assess the quality and integrity of the graft, thus enabling surgeons to identify and address any issues before they lead to significant complications. In this review article, we aim to discuss the strengths and limitations of all available techniques and modalities, with the goal to identify the best modality for evaluating graft patency during and after CABG surgery.

This study investigates the role of DNA methyltransferase 1 (DNMT1) in T cell senescence and heart transplant rejection using mouse models and clinical data. In the mouse heart transplantation model, DNMT1 was found to be highly expressed in graft-infiltrating T cells. Using Dnmt1^flox/floxCd4^cre/+ mice, researchers demonstrated that T cell-specific knockout of DNMT1 led to long-term graft survival by impairing effector differentiation and promoting senescence in CD4⁺ T cells, rather than CD8⁺ T cells. Whole-genome methylation sequencing and RNA sequencing revealed that DNMT1 knockout decreased methylation of the cyclin-dependent kinase inhibitor 1A (CDKN1A) promoter, upregulating CDKN1A expression. Depletion of CDKN1A^high cells reversed DNMT1 inhibitor-induced T cell senescence. Clinically, increased T cell senescence was observed in post-transplant patients and is known to increase with age. Additionally, data from the UNOS database showed lower rejection rates in older recipients (age > 65). These findings suggest that DNMT1 ablation accelerates CD4⁺ T cell senescence by altering CDKN1A methylation, thereby reducing T cell function and mitigating rejection. DNMT1 may thus serve as a potential therapeutic target for heart transplant rejection.

Circadian clocks play important role in immunoregulation. We aimed to investigate cardiac circadian clock specific pathways and compare cardiac grafts procured at different timing on survival after transplantation to explore novel criteria for donor selection. In primate heart, Phase Set Enrichment Analysis (PSEA) showed rhythmic transcripts were enriched in antigen processing and presentation during activation of circadian rhythm. Digital sorting of immune cell composition and Single-sample Gene Set Enrichment Analysis (ssGSEA) in unused donor transcriptomes showed the pathway positive regulation of circadian rhythm significantly correlates with allograft rejection and antigen presentation pathways as well as with increased compositions of matured dendritic cell, CD4⁺ T cell and naive B cell. Single-center retrospective cohort of 390 adult heart transplants between 1st January, 2015 and 31th December, 2020 was used to generate a propensity score matching (PSM) cohort. Survival curve differed significantly showing inferior long-term survival when donor hearts were procured at activation group (12PM to 12AM) compared to repression group (12AM to 12PM) (6-year survival: 64.2% vs 75.8%, P = 0.0065). Activation group was also associated with significantly higher rates of in-hospital death, cardiopulmonary resuscitation and usage of mechanical circulatory support after heart transplantation compared to repression group. Furthermore, tendency for post-transplant free of rejection rates were higher in repression group compared to activation group (acute rejection, Gehan-Breslow P = 0.11 and 0.04; chronic rejection, Log rank P = 0.077 and 0.15, in full and PSM cohort respectively). Adjusted COX analysis showed that activation group was associated with 2.20 times increased hazard of death (HR: 2.20; 95% CI: 1.23-3.95; P = 0.008) compared to repression group. Circadian immunity may represent donor-related risk factors for cardiac allograft rejection through activating genes related to antigen presentation pathway and immune cells oscillation at specific time of day. Molecular circadian clock should be considered during retrieval of cardiac allografts in order to maximize graft durability. The effect of circadian rhythm has not been reported during donor heart procurement. Here we show that heart immunity correlates with circadian rhythm regulatory pathway. Crdiac grafts procured between 12AM to 12PM confers superior long-term survival of recipients. Further understanding of the circadian regulation of immunity in organs can provide novel strategies for preventing graft rejection and maximizing graft durability.

Cardiac valve replacement is an effective method to treat valvular heart disease. Artificial valves used routinely in clinic still have defects. In our study, we explored a novel method to modify the performance of Decellularized Heart Valve (DHV) scaffold. The decellularized porcine aortic valve was prepared using sequential hydrophile and lipophile solubilization method. The sericin was extracted from silk fibroin-deficient silkworm cocoon by lithium bromide method. First, DHV was immersed in sericin solution to produce the sericin–DHV composite scaffold. Then, we modified the DHV by making a Polydopamine (PDA) coating on the DHV first and then binding the sericin. The physical properties and biological compatibility of our composite scaffold were assessed in vitro and in vivo. Sericin were successfully prepared, combined to DHV and improved its biocompatibility. PDA coating further promoted the combination of sericin on DHV and improved the physical properties of scaffolds. The decay rate of our modified valve scaffold was decreased in vivo and it showed good compatibility with blood. In conclusion, our modification improved the physical properties and biocompatibility of the valve scaffold. The combination of PDA and sericin promoted the recellularization of decellularized valves, showing great potential to be a novel artificial valve.

The ischemia–reperfusion process of a donor heart during heart transplantation leads to severe mitochondrial dysfunction, which may be the main cause of donor heart dysfunction after heart transplantation. Pyruvate carboxylase (PC), an enzyme found in mitochondria, is said to play a role in the control of oxidative stress and the function of mitochondria. This research examined the function of PC and discovered the signaling pathways controlled by PC in myocardial IRI. We induced IRI using a murine heterotopic heart transplantation model in vivo and a hypoxia–reoxygenation cell model in vitro and evaluated inflammatory responses, oxidative stress levels, mitochondrial function, and cardiomyocyte apoptosis. In both in vivo and in vitro settings, we observed a significant decrease in PC expression during myocardial IRI. PC knockdown aggravated IRI by increasing MDA content, LDH activity, TUNEL-positive cells, serum cTnI level, Bax protein expression, and the level of inflammatory cytokines and decreasing SOD activity, GPX activity, and Bcl-2 protein expression. PC overexpression yielded the opposite findings. Additional research indicated that reducing PC levels could block the Wnt/β-catenin pathway and glutamine metabolism by hindering the movement of β-catenin to the nucleus and reducing the activity of complex I and complex II, as well as ATP levels, while elevating the ratios of NADP+/NADPH and GSSG/GSH. Overall, the findings indicated that PC therapy can shield the heart from IRI during heart transplantation by regulating glutamine metabolism through the Wnt/β-catenin pathway.