About 50% of cardiac patients do not have typical cardiac risk factors. Therefore, it is important to search for additional factors that may be responsible for heart disease. If these factors are identified, the test could help predict high-risk cardiovascular patients. The studies about the etiology of coronary artery disease have led to the discovery of novel biomarkers. Recently, accumulating evidence has highlighted the critical role of both systemic and localized inflammatory markers accompanied by atherosclerosis and cardiac conditions. Particularly, higher levels of inflammatory biomarkers like CRP can lead to cardiovascular diseases. This article presents an analysis of the causes of heart disease, atherosclerosis, endothelial dysfunction, and plaque rupture, with a special focus on the role of inflammation as a contributing factor. Additionally, the article examines ways to reduce the inflammation associated with cardiovascular disease.

Cardiovascular disease remains the leading cause of mortality worldwide. Although minimally invasive interventions have improved outcomes, open surgical reconstruction using vascular grafts is still required for many patients. Autologous vessels are preferred due to superior elastic modulus and biocompatibility; however, a substantial proportion of patients lack suitable donor vessels. Synthetic grafts perform adequately in large-diameter applications but frequently fail in small-diameter settings (≤6 mm) due to thrombosis, infection, and poor long-term patency. These limitations highlight the need for next-generation arterial grafts and robust preclinical evaluation systems. Here, we present two complementary large-animal in vivo sheep models for systematic assessment of arterial graft safety, functionality and regenerative potential. One model enables implantation of short interposition grafts (≈10 cm) in the carotid artery, while a second, novel configuration accommodates long-segment grafts (≈30 cm) in a carotid-axillary setup. Both models are integrated with a comprehensive analytical framework to evaluate patency, regeneration, biomechanical stability, immune activation and transcriptomic remodeling. Method overview: • Sheep models supporting implantation of short and long arterial grafts under physiological flow • Multimodal evaluation combining imaging, biomechanics, histology, flow cytometry, and transcriptomics • Generic platform for assessing graft functionality, safety and biological characterization.

SARS-CoV-2 infection not only leads to severe respiratory diseases but also has a significant impact on the cardiovascular system, inducing acute cardiac injury and various long-term cardiovascular complications. Non-coding RNAs (ncRNAs), as key molecules in gene expression regulation, exhibit important regulatory roles in viral infections and cardiovascular pathological processes. Current research indicates that ncRNAs such as miRNA, lncRNA, and circRNA participate in the occurrence and development of cardiac injury related to SARS-CoV-2 infection by regulating apoptosis, metabolic reprogramming, and cell communication. However, there are still many challenges and unresolved mysteries regarding their specific regulatory networks and clinical applications. This review systematically summarizes the expression changes and functional characteristics of ncRNAs in COVID-19-related cardiovascular diseases, focusing on their potential as biomarkers and therapeutic targets, and combining the latest multi-omics data and cutting-edge technologies to anticipate the development direction of precise interventions and personalized treatments.

Chuanxiong (Ligusticum chuanxiong Hort.) and Chishao (Paeonia lactiflora Pall.) are widely used in Traditional Chinese Medicine (TCM) for their ability to promote blood circulation and resolve blood stasis, particularly in the treatment of cardiovascular diseases such as atherosclerosis (AS).

This review systematically summarizes the potential mechanisms by which L. chuanxiong and P. lactiflora modulate iron metabolism, inhibit ferroptosis, and enhance blood flow, offering innovative strategies for the treatment of AS.

A comprehensive literature search was performed using databases such as PubMed, Web of Science, and CNKI. We implemented a narrative review with explicit search strategies across regional databases that included specific keywords related to the pharmacological effects of Chuanxiong and Chishao, particularly their roles in iron metabolism and ferroptosis. Studies were selected based on predefined inclusion criteria, ensuring relevance and quality. The data were organized to summarize the mechanisms of action and therapeutic potential of these substances, while also incorporating insights from traditional medical texts, including classical TCM literature. Specific search strategy: SU=(("Atherosclerosis" [MeSH] OR "Atherosclerotic plaque" [Title/Abstract] OR "AS" [Title/Abstract] OR "Arteriosclerosis" [Title/Abstract]) AND ("Chuanxiong" [Title/Abstract] OR "Ligusticum chuanxiong" [MeSH]) AND ("Chishao" [Title/Abstract] OR "Paeonia lactiflora" [MeSH])) AND (("iron metabolism" [Title/Abstract] OR "ferroptosis" [MeSH] OR "lipid peroxidation" [Title/Abstract]) OR ("JAK-STAT pathway" OR "PI3K/AKT" OR "MAPK/NF-κB" OR "GPX4" [Title/Abstract]) AND ("randomized controlled trial" [Publication Type] OR "in vitro" [Title/Abstract] OR "in vivo" [Title/Abstract] OR "clinical study" [Title/Abstract])).

Ligusticum chuanxiong: and P. lactiflora modulate iron homeostasis by suppressing hepcidin and enhancing ferroportin, inhibit ferroptosis via GPX4 activation and System Xc^- upregulation, and mitigate oxidative stress/inflammation through ROS scavenging and NF-κB suppression, collectively reducing atherosclerotic plaque instability.

Chuanxiong and Chishao demonstrate significant potential as therapeutic agents for AS by targeting iron metabolism and ferroptosis. Their traditional use in TCM is supported by modern pharmacological evidence, highlighting their potential for integration into modern therapeutic frameworks.

Arsenic trioxide (ATO) is an effective chemotherapeutic agent but causes severe cardiotoxicity, which limits its clinical application. 10-Gingerol (10Gin) is a major bioactive component of ginger, yet its cardioprotection and the mechanism underlying its effects against ATO-induced heart injury (HI) have not been fully elucidated. This study integrated network pharmacology (NP) analysis, in vivo mouse models, and in vitro cell experiments to investigate the cardioprotection of 10Gin against ATO-induced HI and its underlying mechanisms. NP analysis identified 32 overlapping therapeutic targets of 10Gin, ATO, and HI, among which the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was the most significantly enriched cardiovascular-related pathway. Our in vivo experimental results demonstrated that 10Gin treatment significantly ameliorated ATO-induced histopathological injury and cardiac dysfunction in mice. Echocardiographic evaluation showed that 10Gin improved ATO-induced systolic dysfunction, as evidenced by increased ejection fraction and fractional shortening. Specifically, 10Gin reduced serum levels of myocardial injury markers, enhanced endogenous antioxidant enzyme activities, decreased reactive oxygen species production, downregulated pro-inflammatory cytokine mRNA expression, and inhibited cardiomyocyte apoptosis. In vitro experiments involving H9c2 cells and AC16 human cardiomyocytes showed that 10Gin enhanced cell viability, attenuated apoptosis and oxidative stress, thereby exerting cardioprotective effects. Moreover, 10Gin significantly increased the p-PI3K/PI3K and p-AKT/AKT ratios both in vivo and in vitro. Notably, the in vitro cardioprotection of 10Gin could be partly reversed by the PI3K inhibitor LY294002. These findings indicate that 10Gin alleviates ATO-induced HI through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, which are likely mediated by PI3K/AKT activation, thereby supporting further investigation of 10Gin as a potential adjunctive candidate.

Desmin, a crucial intermediate filament in muscle cells, maintains structural integrity in cardiac muscle and provides stability to striated muscle cells. Mutations in the DES gene lead to desminopathies, causing diverse cardiac and skeletal myopathies. We examine an Iranian family with a highly penetrant p.Arg383His variant in the DES gene, resulting in severe hypertrophic cardiomyopathy (HCM) without skeletal phenotypes. Moreover, we discuss all reported disease-causing missense variants, examining their clinical manifestations across different domains. We assessed demographic data, clinical features, and genetic analysis in members of this Iranian family. Whole genome sequencing (WGS), in silico structural and functional predictions, was also used to investigate genetic entities. Also, a mini-review was performed across various databases to identify all disease-causing missense variants within the DES gene. WGS identified a p.Arg383His variant in the DES gene in the Iranian family. Analyzing 119 disease-causing missense variants in desmin revealed limited correlation between variant location and phenotypes. A significant prevalence (36.9%) of conduction diseases was linked to variants in various domains. Heart failure appeared enriched among variants located in coil2B, while syncope was more frequently reported in variants affecting coil2B and the tail domains; however, these observations are exploratory and literature-derived. Different domains showed varying associations with specific clinical outcomes, such as spine ankylosis in the tail domain and dysphonia in the desmin head domain. The present study reports an Iranian family exhibiting severe HCM due to a likely pathogenic DES gene variant, lacking skeletal myopathy phenotypes. Also, examination of all missense variants highlighted clinical heterogeneity and complex inheritance patterns among individuals carrying different variants in the DES gene. In this context, genetic analysis is a valuable diagnostic tool for effectively managing affected patients, identifying carriers, and facilitating future family planning decisions.

Osteoarthritis (OA) involves cartilage degradation and subchondral bone alterations, yet the mechanisms of chondro-endothelial crosstalk remain unclear. Stress-sensitive Piezo1 and SP1/Angptl7 signaling may play key roles in this process. This research aimed to investigate whether Platelet-derived growth factor (PDGF)-BB regulates chondro-endothelial crosstalk via Piezo1-mediated SP1/Angptl7 inhibition.

Single- and multiple-cell-component organoids (chondrocytes SW1353 and endothelial HMEC-1) were constructed using high-throughput 3D culture. Organoids were treated with MIA to induce OA-like changes, followed by PDGF-BB with or without Yoda1 (Piezo1 activator) or Angptl7. In vivo, OA was induced in rats by intraarticular MIA injection, and PDGF-BB or sodium hyaluronate (SH)-PDGF was administered. Histology and immunofluorescence were used to assess F-actin formation, Piezo1 activation, SP1 phosphorylation, Angptl7 and VEGF/Notch/DLL4 expression.

PDGF-BB inhibited F-actin formation and reduced Piezo1 activation in OA chondrocytes. It suppressed SP1 phosphorylation and Angptl7 expression, downregulating VEGF/Notch/DLL4 signaling and reducing endothelial invasion in organoids. These effects were partially reversed by Yoda1 and fully reversed by Angptl7. In vivo, PDGF-BB and SH-PDGF attenuated cartilage degeneration and reduced Piezo1 activation, SP1 phosphorylation, and Angptl7 expression.

PDGF-BB alleviates OA by inhibiting SP1/Angptl7-mediated chondro-endothelial crosstalk, partially via stress-sensitive Piezo1 regulation through cytoskeletal remodeling. Multiple-cell-component organoids provide a valuable in vitro model for studying cartilage pathophysiology.

Once regarded solely as an intermediate of the tricarboxylic acid (TCA) cycle involved in energy production, fumarate has now emerged as a pivotal immunometabolite with far-reaching effects on inflammatory signaling and immune cell fate. This review comprehensively delineates the dual nature of fumarate, which functions as a context-dependent rheostat of inflammation. Intracellular fumarate levels are tightly regulated by enzymatic activity, transport systems, and exogenous sources, including the pharmacological agent dimethyl fumarate (DMF). Fumarate can covalently modify critical cysteine residues in proteins through a process known as succination. Importantly, DMF acts at supraphysiological concentrations and may engage mechanisms distinct from those associated with endogenously accumulated fumarate. This unique post-translational modification enables fumarate to directly modulate key signaling pathways, including nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (NRF2), hypoxia-inducible factor 1-alpha (HIF-1α), Janus kinase/signal transducer and activator of transcription (JAK-STAT), and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, thereby orchestrating a broad anti-inflammatory program. We further examine how fumarate reshapes the functional phenotypes of macrophages, dendritic cells, T cells, and B cells, ultimately skewing immune responses toward tolerance and resolution. Crucially, this review distinguishes among the physiological roles of endogenous fumarate, the pathological consequences of fumarate accumulation resulting from fumarate hydratase (FH) deficiency, and the pharmacological actions of exogenous fumarate esters. Conversely, dysregulated fumarate metabolism, as observed in conditions such as hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and systemic lupus erythematosus, can paradoxically promote pathological inflammation. The successful clinical translation of fumarate esters, particularly DMF, for the treatment of multiple sclerosis and psoriasis underscores their therapeutic potential. By synthesizing recent advances in fumarate biology, this review not only elucidates its role as a fundamental link between cellular metabolism and immunity but also highlights future directions for targeting fumarate-associated pathways in a broad spectrum of chronic inflammatory diseases.

Chronic kidney disease (CKD), a highly prevalent condition worldwide, is associated with increased thrombotic and bleeding risks. Thrombotic risks include heightened cardiovascular risk and that of venous thromboembolism, driven by endothelial dysfunction, and inflammation. Conversely, platelet dysfunction and vascular abnormalities elevate the bleeding risk. This complex interplay of bleeding and thrombosis highlights the challenges faced in anticoagulant prescribing in CKD. Although warfarin and low-molecular-weight heparin are currently recommended in the guidelines, direct oral anticoagulants (DOACs) may offer a favourable profile in mild-to-moderate CKD based on the decreased incidence of thrombotic events and lower bleeding risk reported in studies. There remains a paucity of studies on DOAC use in severe CKD and end-stage renal disease (ESRD). In this article we discuss different options of anticoagulant use in the setting of CKD for venous thromboembolism (VTE) treatment and prophylaxis in atrial fibrillation (AF), highlighting the need for further clinical trials in this patient population.

Histological examination revealed acute myocardial infarction in the anterior wall and ventricular septum, with in-stent occlusive thrombosis overlying neoatherosclerosis in the left anterior descending artery. Dense neutrophilic infiltration was observed in the ruptured plaque and the media, and neutrophilic endarteritis and plaque erosion were also identified in non-culprit coronary arteries. The findings suggest that sepsis-associated vascular inflammation may promote diffuse coronary endothelial injury and plaque instability.