BackgroundAcute myocardial infarction (AMI), characterized by acute myocardial necrosis due to coronary occlusion, is a life-threatening cardiovascular event. Ferroptosis critically contributes to ischemic injury, yet its causal regulators in AMI, particularly in endothelial cells, remain elusive.MethodsWe integrated AMI transcriptomics with summary-data-based Mendelian randomization (SMR) and colocalization to identify causal ferroptosis-related transcription factor (TF). A miRNA-TF-mRNA regulatory network was constructed via miRNA-TF and TF-target prediction. Subsequent analyses, including TF binding site prediction, GSEA, GeneMANIA, gene-disease and gene-drug association screening, phenome-wide association study (PheWAS), ROC curve evaluation, and RT-qPCR validation in HUVECs, were performed to characterize the molecular mechanisms of this axis in AMI.ResultsEPAS1 was identified as a causal ferroptosis-related TF in AMI (PSMR < 0.05; PHEIDI > 0.05). We constructed a ferroptosis-related miRNA-TF-mRNA network and identified a novel endothelial-specific axis, hsa-miR-138-5p/EPAS1/BACH1. RT-qPCR in HUVECs validated the GEO-derived expression patterns of axis components. PheWAS further revealed no significant adverse phenotypic associations for genes within this axis, supporting the druggability of approved compounds targeting it.ConclusionThis study identifies EPAS1 as a TF with suggestive genetic links to AMI risk and characterizes a novel endothelial-enriched hsa-miR-138-5p/EPAS1/BACH1 regulatory axis governing ferroptosis. This molecular cascade provides candidate molecular clues for subsequent preclinical research into cardioprotective strategies targeting ferroptosis in AMI.

Clonal hematopoiesis of indeterminate potential (CHIP), commonly involving TET2 and DNMT3A mutations, is increasingly recognized as a cardiovascular risk factor, but its prognostic role in severe aortic valve stenosis (AVS) remains unclear. This study aimed to systematically evaluate the impact of CHIP on survival in AVS patients undergoing valve replacement. A systematic search of PubMed, Embase, Web of Science, and Scopus through May 2025 identified observational studies of CHIP in AVS patients undergoing valve replacement. Eligible studies used validated genomic sequencing methods to identify CHIP and reported mortality outcomes. Two reviewers independently extracted study characteristics, outcomes, and related variables. Pooled hazard ratios (HRs) were calculated, with subgroup analyses by mutation type and geographic region, and meta-regression to assess effect modifiers. Risk of bias was assessed using the Newcastle–Ottawa Scale, and sensitivity and publication bias analyses were also assessed. Five studies with 1,175 patients were included. CHIP showed a non-significant trend toward increased all-cause mortality (HR = 1.58; 95

BACKGROUND:Hyperlipidemia (HLP) exacerbates myocardial cell injury by impairing lipophagy, a crucial lipid metabolic process, thereby increasing the risk of acute myocardial infarction (AMI). This study aims to identify biomarkers associated with HLP and lipophagy that are relevant to AMI risk through a combined transcriptomic and Mendelian randomization (MR) approach. METHODS:mRNA expression data for AMI, along with genes related to HLP (HRGs) and lipophagy (LRGs), were obtained from public databases. Biomarkers were identified using differential expression analysis, weighted gene co-expression network analysis (WGCNA), MR analysis, and receiver operating characteristic (ROC) analysis, augmented by two machine learning algorithms and expression validation. These biomarkers were further used to explore the role of platelet activation-related genes (PARGs) in AMI, with enrichment analysis providing insights into their underlying mechanisms. Expression of selected biomarkers was validated in clinical samples using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS:Three biomarkers consistently exhibited significant upregulation in AMI samples, which was confirmed by RT-qPCR. Specifically, PLAUR [Odds ratio (OR) = 1.115, 95 % confidence interval (CI): 1.006-1.237, P = 0.038] and IVNS1ABP (OR = 1.047, 95 % CI: 1.000-1.096, P = 0.048) were identified as AMI risk factors, while QKI (OR = 0.946, 95 % CI: 0.903-0.991, P = 0.020) was recognized as a protective factor. PLAUR, QKI, and IVNS1ABP demonstrated strong diagnostic performance with area under the curve (AUC) values of 0.773, 0.933, and 0.807, respectively. When combined in a nomogram, the AUC reached 0.924. These genes were primarily enriched in pathways related to cardiovascular diseases, inflammation, and cellular metabolism, and were notably linked to platelet activation, as evidenced by their strong associations with PARGs. CONCLUSION:In conclusion, the biomarkers PLAUR, QKI, and IVNS1ABP, associated with HLP and lipophagy, exhibit a potential causal relationship with AMI and significant diagnostic potential for predicting AMI risk, providing valuable insights for clinical diagnostics and AMI research.

BackgroundHypertrophic Cardiomyopathy (HCM) is an inherited heart disease and the pathogenesis of HCM involves genetic mutations, hemodynamic stress, and metabolic factors, with myocardial fibrosis playing a crucial role in severe clinical events. IL-33/ST2 signaling pathway known for its roles in immune response and tissue repair, participates in cardiac protection and anti-cardiac fibrosis in heart failure. The role of ST2 in HCM remains unclear, and IL-33/ST2 pathway and broader inflammatory responses may be critical in HCM.MethodsWe re-analyzed RNA sequencing data from 9 high-throughput sequencing datasets comprising myocardial tissue samples from 109 HCM patients and 210 non-HCM controls. Differential gene expression analysis, correlation analyses, and Gene Set Enrichment Analysis (GSEA) were employed to explore the biological significance of ST2-related genes and the IL-33/ST2 pathway. Immune infiltration was assessed using CIBERSORTx, and protein-protein interaction networks were constructed using the STRING database.ResultsOur analysis identified 2,660 upregulated and 403 downregulated genes for HCM in the combined dataset, with significant downregulation of the ST2 gene (log2 fold change = −5.0, adjusted P-value = 9.2 × 10−¹⁴³). This downregulation was consistently observed across multiple individual studies. Correlation analysis revealed significant positive correlations between ST2 and key inflammatory mediators such as IL6 and CD163. GSEA highlighted the enrichment of pathways related to immune response, inflammation, and cardiac morphogenesis, with notable upregulation of pro-inflammatory pathways. Immune infiltration analysis revealed a significant inverse correlation between ST2 expression and regulatory T cells (r = −0.34) and a positive correlation with neutrophils (r = 0.39). Pathway analysis indicated ST2's key role in networks involving inflammatory and fibrotic responses.ConclusionsOur findings suggest that downregulation of ST2 in HCM may be associated with a dysregulated inflammatory gene network, potentially contributing to myocardial fibrosis and remodeling. These results highlight the possible critical role of the IL-33/ST2 pathway in disease progression, offering a potential therapeutic target for managing inflammation and fibrosis in HCM.

Background: Hyperlipidemia (HLP) may intensify myocardial cell damage by disrupting lipophagy, a pivotal lipid metabolism pathway, thereby heightening the risk of acute myocardial infarction (AMI). This study aims to identify HLP- and lipophagy-associated biomarkers for AMI through a combined transcriptomic and Mendelian randomization (MR) approach. Methods: The mRNA expression data for AMI, along with HLP-related genes (HRGs) and lipophagy-related genes (LRGs), were sourced from public databases. Biomarkers were identified by conducting differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), MR analysis, and Receiver Operating Characteristic (ROC) analysis, complemented by two machine learning algorithms and expression validation. These biomarkers facilitated an investigation into the role of platelet activation-related genes (PARGs) in AMI, with enrichment analysis providing insights into their underlying mechanisms. Finally, reverse transcription-polymerase chain reaction (RT-PCR) was employed to validate biomarker expression in clinical samples. Results: Three biomarkers exhibited a consistently significant upregulation trend in AMI samples, corroborated by RT-qPCR findings. Notably, PLAUR [Odds Ratio (OR) = 1.115, 95% confidence interval (CI): 1.006-1.237, P = 0.038] and IVNS1ABP (OR = 1.047, 95% CI: 1.000-1.096, P = 0.048) emerged as AMI risk factors, while QKI (OR = 0.946, 95% CI: 0.903-0.991, P = 0.020) was identified as a protective factor. Additionally, PLAUR, QKI, and IVNS1ABP demonstrated robust diagnostic efficacy with Area Under the Curve (AUC) values of 0.773, 0.933, and 0.807, respectively; when integrated into a nomogram, the combined AUC reached 0.924. These genes were enriched in pathways linked to cardiovascular diseases, inflammatory responses, and cellular metabolic processes and appeared actively involved in platelet activation, as indicated by their strong associations with PARGs. Conclusion: In summary, the biomarkers PLAUR, QKI, and IVNS1ABP, connected to HLP and lipophagy, showed a causal relationship with AMI and marked diagnostic potential for predicting AMI risk, offering valuable support for clinical diagnostics and AMI research. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Grants from the National Natural Science Foundation of China (82360077, 82460065), 535 Talent Project of First Affiliated Hospital of Kunming Medical University (2024535Q03), Yunnan Fundamental Research Projects (202201AU070063), Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University (202201AY070001-082). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of the First Affiliated Hospital of Kunming Medical University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

Cardiac Vascular disease particularly myocardial infarction (MI) is a threat to health worldwide. microRNAs (miRNAs) have been shown to regulate myocardial fibrosis. Therefore, it is potential to investigate the mechanism of miRNA and fibrosis following myocardial infarction. Hypoxia human cardiac microvascular endothelial cells (HCMECs) were selected for the vitro experimental model. The miR-146a-5p expression was tested via RT-qPCR. The level of endothelial-to-mesenchymal transition (EndMT) and fibrosis markers were detected by Western blotting and immunofluorescence. Then, the inflammation, cell viability and apoptosis were investigated. The target was predicted by an online database and verified by a dual-luciferase activity assay. An MI mouse model was created to validate that miR-146a-5p regulates cardiac fibrosis in vivo. MI mouse was transfected with miR-146a-5p lentivirus. Subsequently, its effect on cardiac fibrosis of infarcted hearts was assessed by In situ hybridization (ISH), Immunohistochemistry (IHC), Triphenylterazolium chloride (TTC) staining and Masson staining. Herein, we confirmed that miR-146a-5p was down-regulated in hypoxia HCMECs. Overexpression of miR-146a-5p inhibited hypoxia-induced cardiac fibrosis following myocardial infarction by inhibiting EndMT in HCMECs. Thioredoxin-interacting protein (TXNIP) was a target that was negatively regulated by miR-146a-5p. Up-regulation of miR-146a-5p inhibited cardiac fibrosis via regulating EndMT by targeting TXNIP, and it also regulated EndMT to inhibit cardiac fibrosis in vivo.

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo.Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR).Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice.Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

目的 探讨癌胚抗原相关细胞黏附分子(CEACAM1)源性多肽KM17对血小板聚集、释放、黏附功能的影响.方法 采用血小板聚集仪观察多肽KM17对凝血酶、胶原、花生四烯酸(AA)、二磷酸腺苷(ADP)等激动剂诱导的血小板聚集的影响;流式细胞术观察多肽KM17对ADP激活血小板后P-选择素释放的影响;显微镜下观察多肽KM17对血小板静态黏附于胶原基质的影响.结果 多肽KM17能显著促进ADP诱导的血小板聚集且呈剂量依赖(P<0.05),而对AA、胶原及凝血酶诱导的血小板聚集差异均无统计学意义(P>0.05);此外,多肽KM17对ADP激活血小板后P-选择素释放及血小板静态黏附于胶原基质的差异也无统计学意义(P>0.05).结论 多肽KM17可明显促进ADP诱导的血小板聚集,但对ADP活化血小板后P-选择素释放及血小板静态黏附于胶原基质未见明显作用.

Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.

Purpose: To investigate the underlying mechanism of cardiomyocyte protection of carvedilol based on autophagy and apoptosis. Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to various concentrations of carvedilol before anoxia, and pretreated with 3-MA or compound C for inhibiting autophagy or p-AMPK expression. CCK-8 colorimeter and flow cytometry were used to determine the cell viability and apoptotic rates. The variation of mRNA and protein was measured by RT-PCR and Western blot. The presence of autophagosomes was observed by electron microscopy. Results: First, we found that carvedilol increased autophagic marker levels in a concentration-dependent manner and the number of autophagosomes in NRVMs. Moreover, carvedilol substantially enhanced the viability and noticeably reduced the CK, MDA and LDH levels and cell apoptosis rate compared with the anoxia group. In addition, carvedilol decreased the levels of caspase-3 and Bim in mRNA and protein, but such effect was blocked by the special autophagy inhibitor-3-MA, and the number of autophagosomes was significantly decreased when treated with 3-MA, indicating that carvedilol exhibited anti-apoptotic and anti-injury effects by inducing autophagy in anoxia NRVMs, but these effects can be abolished by adding 3-MA to suppress autophagy. Finally, the carvedilol treatment-induced autophagy by enhancing the activation of p-AMPK and inhibiting p-mTOR. Electron microscopy presented that the number of autophagosomes was significantly decreased when treating with compound C, indicating that carvedilol induced autophagy in anoxia NRVMs partly by the AMPK-mTOR signaling pathway. Conclusions: Carvedilol has cardioprotection by inducing autophagy against apoptosis partly through the AMPK/mTOR pathway during anoxia in NRVMs.

Background: Circulating microRNAs (miRNAs) have emerged as potential biomarkers for cardiovascular diseases. However, few studies have focused on the role of exosomal miRNAs in acute coronary syndrome (ACS). The purpose of this study was to explore weather serum exosomal microRNA-146a (exo-miR-146a) could be used as a novel diagnostic biomarker for ACS and to investigate its relationship with inflammatory response. Methods: A total of 63 ACS patients and 25 patients with normal coronary arteries (Control) were enrolled respectively. The serum exosomes were isolated and then identified by transmission electron microscopy (TEM), western blot, and nanoparticle tracking analysis (NTA). The expression levels of exo-miR-146a in serum were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and the expression levels of interleukin-10 (IL-10), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to appraise the potential factors related to serum exo-miR-146a and receiver operating characteristic (ROC) curve analysis was applied for predicting the accuracy of ACS via the area under curve (AUC). Results: Exosomes isolated from serum were of typical cup-like shape, with 50-150 nm diameter, and expressed CD9, CD63, CD81, and HSP70. The expression levels of serum exo-miR-146a, IL-10, IL 6, and TNF-alpha were significantly increased in ACS patients compared with the control group, Spearman ' s correlation analysis indicated that exo-miR-146a expression was markedly positively correlated with IL 10, IL-6, and TNF-alpha. The ROC curve analyses revealed that exo-miR-146a could distinguish ACS patients from their normal controls. Conclusions: The serum exo-miR-146a may be used as a novel diagnostic biomarker for ACS patients, and it is also associated with inflammatory response.

Atherosclerosis (AS) is the most common and serious complication in type 2 diabetes mellitus (T2DM). Recent studies have emphasized that inflammation is the main cause of atherosclerosis. Studies have shown that carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) regulates the expression of matrix metallopeptidase 9 (MMP-9) after ischemic stroke to reduce inflammation. The aim of this study was to elucidate potential molecular mechanism of CEACAM1 on the inflammatory response in atherosclerosis. The serum levels of CEACAM1, MMP-9, and tissue inhibitors of metalloproteinase 1 (TIMP-1) in T2DM patients and healthy control was detected. The results showed that the levels of CEACAM1 and TIMP-1 were significantly decreased, and the levels of MMP-9 were significantly higher than those in the control group. Moreover, we also observed the effect of CEACAM1 on atherosclerosis in T2DM rats. Hematoxylin & eosin (HE) staining and oil red staining showed that CEACAM1 recombinant protein reduced intima-media thickness and the area of atherosclerotic plaques. To further explore the molecular mechanism of CEACAM1 regulating MMP-9/TIMP-1, we conducted experiments in rat aorta vascular endothelial cells and rat aorta smooth muscle cells. The result showed that CEACAM1 inhibits inflammatory response via MMP-9/TIMP-1 axis. Taken together, CEACAM1 attenuates diabetic atherosclerosis by inhibition of IκB/NF-κB signal pathway via MMP-9/TIMP-1 axis, which indicate that CEACAM1 is potentially amenable to therapeutic manipulation for clinical application in atherosclerosis in T2DM.

ABSTRACTCarcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates collagen-mediated platelet activation through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). However, the function of CEACAM1’s extracellular cleavage fragments is currently unknown. In the present study, we used mass spectrometry (MS) to identify 9 cleavage fragments shed by matrix metallopeptidase 12 (MMP-12), and then we synthesized peptides with sequences corresponding to the fragments. QLSNGNRTLT (QLSN), a peptide from the A1-domain of CEACAM1, significantly attenuated collagen-induced platelet aggregation. QLSN also attenuated platelet static adhesion to collagen. Additionally, QLSN reduced human platelet secretion and integrin αIIbβ3 activation in response to glycoprotein VI (GPVI)–selective agonist, convulxin. Correspondingly, QLSN treatment significantly decreased convulxin-mediated phosphorylation of Src, protein kinase B (Akt), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) in human platelets. These data indicate that the CEACAM1-derived peptide QLSN inhibits GPVI-mediated human platelet activation. QLSN could potentially be developed as a novel antiplatelet agent.

Background: Acute coronary syndrome (ACS) occurs approximately every 40 seconds, and was an underlying cause of death in 1 out of every 7 deaths. More accurate indicators are needed to distinguish patients with ACS from patients manifesting negative changes in electrocardiogram (ECG) and myocardial enzymes. This study aimed to investigate whether the expression of platelet carcinoembryonic antigen cell adhesion molecule-5 (CEACAM5/CEA/CD66e) could help predict ACS. Material/Methods: We enrolled 82 participants (mean age 60 years, 33 females and 49 males). The expression of CEA on washed human platelets was assessed using two-color flow cytometry. The CEA levels on platelets and in serum of these 82 consecutive patients were detected using two-color whole-blood flow cytometry analysis and a custom-made Luminex multiplex assay, respectively. Results: CEA was expressed on the surface of human platelets. The expression of platelet CEA (P<0.01), but not serum CEA (P=0.30), was significantly higher in patients with ACS compared to patients with normal coronary artery. Increased platelet CEA levels could serve as a new independent indicator for ACS (P=0.0003). Platelet CEA testing (P=0.000002), as well as cardiac troponin I (cTnI) (P=0.0005), can diagnose ACS with high sensitivity and specificity, and, combined with cTnI (P<0.0001), can improve the diagnostic value. Conclusions: Platelet CEA expression was higher in individuals presenting with ACS. Hence, platelet CEA might be a novel and reliable biomarker for ACS. Large-scale studies are needed to confirm this hypothesis.

Background: Xinmailong (XML), a bioactive composite extracted from Periplaneta americana, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects. Methods: The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed in vivo using an acute pulmonary thrombosis mouse model. Results: XML dose-dependently inhibited in vitro platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited in vivo thrombus formation in a collagen-epinephrine-induced acute pulmonary thrombosis mouse model. Conclusions and General Significance: Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.

Matrix metalloproteinases-12 (MMP12) can lead to degradation of elastin resulting in plaque destabilization and rupture. MMP12 also facilitates platelet aggregation, adhesion, and granule secretion. However, evidence in the literature related to the function of MMP12 in ST-segment elevation myocardial infarction (STEMI) is little. This study investigated the expression of MMP12 in human coronary thrombus and examined the relationship between plasma MMP12 and STEMI. Arterial plasma was obtained from 46 STEMI patients and 52 stable angina pectoris (SAP) patients and 30 controls with angiographically normal coronary arteries. Coronary thrombi were obtained from 26 STEMI patients with a large thrombus burden (LTB). The expression levels of MMP12 in coronary thrombus were analyzed by immunohistochemistry and immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and casein zymography. In addition, MMP12 concentration measured by enzyme-linked immunosorbent assay (ELISA) and activity measured by fluorescence resonance energy transfer (FRET) were used to assess the levels in plasma. We confirmed the expression of MMP12 in human coronary thrombus. MMP12 was secreted mainly in active form of 45kDa in coronary thrombus. In plasma samples of the STEMI group, MMP12 concentrations were found to be higher than the SAP group (5.030 +/- 2.24pg/mL vs 3.010 +/- 1.99 pg/mL, P<.05) but with lower MMP12 activity (332 +/- 77RFU vs 458 +/- 91RFU, P<.05). Also, the STEMI group demonstrated much higher MMP12 concentrations than the normal coronary artery control group (5.030 +/- 2.24 pg/mL vs 1.720 +/- 0.51pg/mL, P<.05) and with lower MMP12 activity (332 +/- 77RFU vs 549 +/- 112RFU, P<.05). In addition, the STEMI group had significantly higher tissue inhibitor of metalloproteinases-1 (TIMP1) concentration (573.40 +/- 270.60pg/mL) than SAP group (384.50 +/- 147.70pg/mL) and control group (219.90 +/- 154.80pg/mL, P<.05). The imbalance in MMP12/TIMP ratio was observed in the STEMI group compared with SAP and control group (P<.05). This study demonstrated that MMP12 exists in human coronary thrombus. Patients with STEMI have elevated plasma level of MMP12 and the imbalance of MMP12/TIMP1. These data supported that MMP12 might be of potential relevance in STEMI.