Cardiac aging: from hallmarks to therapeutic opportunities.

Cardiac aging is an intricate and multifaceted process with considerable impact on public health, especially given the global demographic shift towards aged populations. This review discusses structural, cellular and functional changes associated with cardiac aging and heart failure with preserved ejection fraction (HFpEF). Key molecular mediators are considered within the framework of the established hallmarks of aging, with particular attention to promising therapeutic candidates. We further delineate the differential impacts of aging on cardiac structure and function in men and women, addressing hormonal and chromosomal influences. The protective and mitigating effects of exercise in cardiac aging and HFpEF in particular are discussed, as an inspiration for the identification of pathways that mitigate biological aging. We also emphasize how much remains to be learned and the importance of these efforts in enhancing the cardiac health of aging populations worldwide.

NagZ modulates the virulence of E. cloacae by acting through the gene of unknown function, ECL_03795.

ß-N-acetylglucosaminidase (NagZ), a cytosolic glucosaminidase, plays a pivotal role in peptidoglycan recycling. Previous research demonstrated that NagZ knockout significantly eradicated AmpC-dependent ß-lactam resistance in Enterobacter cloacae. However, NagZ's role in the virulence of E. cloacae remains unclear. Our study, incorporating data on mouse and Galleria mellonella larval mortality rates, inflammation markers, and histopathological examinations, revealed a substantial reduction in the virulence of E. cloacae following NagZ knockout. Transcriptome sequencing uncovered differential gene expression between NagZ knockout and wild-type strains, particularly in nucleotide metabolism pathways. Further investigation demonstrated that NagZ deletion led to a significant increase in cyclic diguanosine monophosphate (c-di-GMP) levels. Additionally, transcriptome sequencing and RT-qPCR confirmed significant differences in the expression of ECL_03795, a gene with an unknown function but speculated to be involved in c-di-GMP metabolism due to its EAL domain known for phosphodiesterase activity. Interestingly, in ECL_03795 knockout strains, a notable reduction in the virulence was observed, and virulence was rescued upon complementation with ECL_03795. Consequently, our study suggests that NagZ's function on virulence is partially mediated through the ECL_03795→c-di-GMP pathway, providing insight into the development of novel therapies and strongly supporting the interest in creating highly efficient NagZ inhibitors.

Endophytic bacteria for Cd remediation in rice: Unraveling the Cd tolerance mechanisms of Cupriavidus metallidurans CML2.

The utility of endophytic bacteria in Cadmium (Cd) remediation has gained significant attention due to their ability to alleviate metal-induced stress and enhance plant growth. Here, we investigate C. metallidurans CML2, an endophytic bacterial strain prevalent in rice, showing resilience against 2400 mg/L of Cd(II). We conducted an in-depth integrated morphological and transcriptomic analysis illustrating the multifarious mechanisms CML2 employs to combat Cd, including the formation of biofilm and CdO nanoparticles, upregulation of genes involved in periplasmic immobilization, and the utilization of RND efflux pumps to extract excess Cd ions. Beyond Cd, CML2 exhibited robust tolerance to an array of heavy metals, including Mn2+, Se4+, Ni2+, Cu2+, and Hg2+, demonstrating effective Cd(II) removal capacity. Furthermore, CML2 has exhibited plant growth-promoting properties through the production of indole-3-acetic acid (IAA) at 0.93 mg/L, soluble phosphorus compounds at 1.11 mg/L, and siderophores at 22.67%. Supportively, pot experiments indicated an increase in root lengths and a decrease in Cd bioaccumulation in rice seedlings inoculated with CML2, consequently reducing Cd translocation rates from 43% to 31%. These findings not only contribute to the understanding of Cd resistance mechanisms in C. metallidurans, but also underscore CML2's promising application in Cd remediation within rice farming ecosystems.

PCT, IL-6, and IL-10 facilitate early diagnosis and pathogen classifications in bloodstream infection.

BACKGROUND: In the diagnosis of bloodstream infection (BSI), various inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL), white blood cell count (WBC), neutrophil percentage (NE%), platelet count (PLT), and erythrocyte sedimentation rate (ESR) have been extensively utilized. However, their specific roles in distinguishing BSI from local bacterial infection (LBI) and in classifying BSI pathogens remain uncertain. METHODS: A historical cohort study was conducted, involving the enrollment of 505 patients with BSI and 102 patients with LBI. To validate the reliability of the clinical data obtained from this cohort, mouse models of BSI were utilized. RESULTS: Our findings revealed that patients with BSI had significantly higher levels of inflammatory markers, including CRP, PCT, IL-6, IL-10, WBC, NE%, and ESR, compared to those with LBI (p < 0.05). The receiver operating characteristic (ROC) curve analysis demonstrated that CRP, PCT, IL-6, IL-10, ESR and NE% exhibited excellent diagnostic efficacy for BSI. Additionally, we observed significant differences in CRP, PCT, IL-6, and IL-10 levels between patients with BSI caused by Gram-positive bacteria (GP-BSI) and Gram-negative bacteria (GN-BSI), but no significant variations were found among specific bacterial species. Furthermore, our study also found that CRP, PCT, and IL-10 have good discriminatory ability for vancomycin-resistant Enterococcus (VRE), but they show no significant diagnostic efficacy for other multidrug-resistant organisms (MDROs) such as carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA). In our mouse model experiments, we observed a remarkable increase in PCT, IL-6, and IL-10 levels in mice with GN-BSI compared to those with GP-BSI. CONCLUSION: Our study has confirmed that PCT, IL-6, and IL-10 are efficient biomarkers for distinguishing between BSI and LBI. Furthermore, they can be utilized to classify BSI pathogens and differentiate between VRE and vancomycin-susceptible Enterococcus. These findings are extremely valuable for clinicians as they enable timely initiation of empiric antibiotic therapies and ultimately lead to improved clinical outcomes for patients with BSI.

Application of Hydrogels in Cardiac Regeneration.

Myocardial infarction (MI) is a leading cause of death globally. Due to limited cardiac regeneration, infarcted myocardial tissue is gradually replaced by cardiac fibrosis, causing cardiac dysfunction, arrhythmia, aneurysm, free wall rupture, and sudden cardiac death. Thus, the development of effective methods to promote cardiac regeneration is extremely important for MI treatment. In recent years, hydrogels have shown promise in various methods for cardiac regeneration. Hydrogels can be divided into natural and synthetic types. Different hydrogels have different features and can be cross-linked in various ways. Hydrogels are low in toxicity and highly stable. Since they have good biocompatibility, biodegradability, and transformability, moderate mechanical properties, and proper elasticity, hydrogels are promising biomaterials for promoting cardiac regeneration. They can be used not only as scaffolds for migration of stem cells, but also as ideal carriers for delivery of drugs, genetic materials, stem cells, growth factors, cytokines, and small molecules. In this review, the application of hydrogels in cardiac regeneration during or post-MI is discussed in detail. Hydrogels open a promising new area in cardiac regeneration for treating MI.

Transcriptome Analyses Revealed the Wax and Phenylpropanoid Biosynthesis Pathways Related to Disease Resistance in Rootstock-Grafted Cucumber.

Cucumbers (Cucumis sativus L.) are a global popular vegetable and are widely planted worldwide. However, cucumbers are susceptible to various infectious diseases such as Fusarium and Verticillium wilt, downy and powdery mildew, and bacterial soft rot, which results in substantial economic losses. Grafting is an effective approach widely used to control these diseases. The present study investigated the role of wax and the phenylpropanoid biosynthesis pathway in black-seed pumpkin rootstock-grafted cucumbers. Our results showed that grafted cucumbers had a significantly higher cuticular wax contents on the fruit surface than that of self-rooted cucumbers at all stages observed. A total of 1132 differently expressed genes (DEGs) were detected in grafted cucumbers compared with self-rooted cucumbers. Pathway enrichment analysis revealed that phenylpropanoid biosynthesis, phenylalanine metabolism, plant circadian rhythm, zeatin biosynthesis, and diterpenoid biosynthesis were significantly enriched. In this study, 1 and 13 genes involved in wax biosynthesis and the phenylpropanoid biosynthesis pathway, respectively, were up-regulated in grafted cucumbers. Our data indicated that the up-regulated genes in the wax and phenylpropanoid biosynthesis pathways may contribute to disease resistance in rootstock-grafted cucumbers, which provides promising targets for enhancing disease resistance in cucumbers by genetic manipulation.

Effects of Reduced Phosphate Fertilizer and Increased Trichoderma Application on the Growth, Yield, and Quality of Pepper.

Phosphorus utilization by crop plants is often limited, thereby resulting in large accumulations of residual phosphorus fertilizer in the soil. Trichoderma fungi function as natural decomposition agents that can contribute to increasing decomposition and promoting nutrient absorption in plants. In this study, we developed a novel fertilizer application strategy that reduces phosphate fertilizer and increases Trichoderma and examined its effects on the growth, nutrient absorption, and fruit quality of pepper (Capsicum annuum L.). We compared the efficacies of eight treatments: P100 = standard dose application of phosphorus fertilizer; P85 = 85% dose; P70 = 70% dose; P0 = no phosphorus fertilizer; and the TP100, TP85, TP70, and TP0 treatments, in which a Trichoderma mixture was added to the P100, P85, P70, and P0 treatments, respectively. The combined fertilizer application strategy stimulated plant growth, increased chlorophyll content, improved yield, and enhanced nutrient absorption. Additionally, the strategy improved pepper fruit quality by increasing the contents of soluble proteins, soluble sugars, vitamin C, capsaicin, and capsanthin. A comprehensive analysis indicated that the TP85 treatment was the optimal fertilization regime for pepper. This study provides a novel fertilizer application strategy for pepper that not only ensures good plant growth but also protects soil health.

Integrated Metabolome and Transcriptome Analysis Provides New Insights into the Glossy Graft Cucumber Fruit (Cucumis sativus L.).

Cucumber is an important vegetable crop, and grafts often affect the quality and wax loss in cucumber fruit and affect its value. However, their metabolites and molecular mechanisms of action remain unclear. Metabolome and transcriptome analyses were conducted on the fruit peels of self-rooted plants (SR) grafted with white seed pumpkin (WG). The results showed that there were 352 differential metabolites in the fruit peels of the SR and WG. The transcriptome analysis showed 1371 differentially expressed genes (DEGs) between the WG and SR. These differentially expressed genes were significantly enriched in plant hormone signal transduction, cutin, suberin, wax biosynthesis, phenylpropanoid biosynthesis, and zeatin biosynthesis. By analyzing the correlation between differential metabolites and differentially expressed genes, six candidate genes related to the synthesis of glycitein, kaempferol, and homoeriodictyol were identified as being potentially important. Key transcription factors belonging to the TCP and WRKY families may be the main drivers of transcriptional changes in the peel between the SR and WG. The results of this study have provided a basis for the biosynthesis and regulation of wax loss and quality in grafted cucumbers and represents an important step toward identifying the molecular mechanisms of grafting onto cucumber fruit.

Promising Therapeutic Treatments for Cardiac Fibrosis: Herbal Plants and Their Extracts.

Cardiac fibrosis is closely associated with multiple heart diseases, which are a prominent health issue in the global world. Neurohormones and cytokines play indispensable roles in cardiac fibrosis. Many signaling pathways participate in cardiac fibrosis as well. Cardiac fibrosis is due to impaired degradation of collagen and impaired fibroblast activation, and collagen accumulation results in increasing heart stiffness and inharmonious activity, leading to structure alterations and finally cardiac function decline. Herbal plants have been applied in traditional medicines for thousands of years. Because of their naturality, they have attracted much attention for use in resisting cardiac fibrosis in recent years. This review sheds light on several extracts from herbal plants, which are promising therapeutics for reversing cardiac fibrosis.

Cryo-EM structure of the polyphosphate polymerase VTC reveals coupling of polymer synthesis to membrane transit.

The eukaryotic vacuolar transporter chaperone (VTC) complex acts as a polyphosphate (polyP) polymerase that synthesizes polyP from adenosine triphosphate (ATP) and translocates polyP across the vacuolar membrane to maintain an intracellular phosphate (Pi ) homeostasis. To discover how the VTC complex performs its function, we determined a cryo-electron microscopy structure of an endogenous VTC complex (Vtc4/Vtc3/Vtc1) purified from Saccharomyces cerevisiae at 3.1 Å resolution. The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3, and three Vtc1 subunits. The transmembrane region forms a polyP-selective channel, likely adopting a resting state conformation, in which a latch-like, horizontal helix of Vtc4 limits the entrance. The catalytic Vtc4 central domain is located on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. The SPX domain of the catalytic Vtc4 subunit positively regulates polyP synthesis by the VTC complex. The noncatalytic Vtc3 regulates VTC through a phosphorylatable loop. Our findings, along with the functional data, allow us to propose a mechanism of polyP channel gating and VTC complex activation.

Integrated Physiological and Transcriptomic Analyses Revealed Improved Cold Tolerance in Cucumber (Cucumis sativus L.) by Exogenous Chitosan Oligosaccharide.

Cucumber (Cucumis sativus L.), sensitive to cold stress, is one of the most economically important vegetables. Here, we systematically investigated the roles of exogenous glycine betaine, chitosan, and chitosan oligosaccharide in alleviating cold stress in cucumber seedlings. The results showed that 50 mg·L-1 chitosan oligosaccharide had the best activity. It effectively increases plant growth, chlorophyll content, photosynthetic capacity, osmotic regulatory substance content, and antioxidant enzyme activities while reducing relative electrical conductivity and malondialdehyde levels in cucumber seedlings under cold stress. To reveal the protective effects of chitosan oligosaccharide in cold stress, cucumber seedlings pretreated with 50 mg·L-1 chitosan oligosaccharide were sampled after 0, 3, 12, and 24 h of cold stress for transcriptome analysis, with distilled water as a control. The numbers of differentially expressed genes in the four comparison groups were 656, 1274, 1122, and 957, respectively. GO functional annotation suggested that these genes were mainly involved in "voltage-gated calcium channel activity", "carbohydrate metabolic process", "jasmonic acid biosynthetic", and "auxin response" biological processes. KEGG enrichment analysis indicated that these genes performed important functions in "phenylpropanoid biosynthesis", "MAPK signaling pathway-plant", "phenylalanine metabolism", and "plant hormone signal transduction." These findings provide a theoretical basis for the use of COS to alleviate the damage caused by cold stress in plant growth and development.

Analysis and Characterization of Glutathione Peroxidases in an Environmental Microbiome and Isolated Bacterial Microorganisms.

Glutathione peroxidases (Gpx) are a group of antioxidant enzymes that protect cells or tissues against damage from reactive oxygen species (ROS). The Gpx proteins identified in mammals exhibit high catalytic activity toward glutathione (GSH). In contrast, a variety of non-mammalian Gpx proteins from diverse organisms, including fungi, plants, insects, and rodent parasites, show specificity for thioredoxin (TRX) rather than GSH and are designated as TRX-dependent peroxiredoxins. However, the study of the properties of Gpx in the environmental microbiome or isolated bacteria is limited. In this study, we analyzed the Gpx sequences, identified the characteristics of sequences and structures, and found that the environmental microbiome Gpx proteins should be classified as TRX-dependent, Gpx-like peroxiredoxins. This classification is based on the following three items of evidence: i) the conservation of the peroxidatic Cys residue; ii) the existence and conservation of the resolving Cys residue that forms the disulfide bond with the peroxidatic cysteine; and iii) the absence of dimeric and tetrameric interface domains. The conservation/divergence pattern of all known bacterial Gpx-like proteins in public databases shows that they share common characteristics with that from the environmental microbiome and are also TRX-dependent. Moreover, phylogenetic analysis shows that the bacterial Gpx-like proteins exhibit a star-like radiating phylogenetic structure forming a highly diverse genetic pool of TRX-dependent, Gpx-like peroxidases.

Application of Single-Cell Genomics in Cardiovascular Research.

Cardiovascular diseases (CVDs) are the leading cause of death in the global world. The emergence of single-cell technologies has greatly facilitated the research on CVDs. Currently, those single-cell technologies have been widely applied in atherosclerosis, myocardial infarction, cardiac ischemia-reperfusion injury, arrhythmia, hypertrophy cardiomyopathy, and heart failure, which are extremely helpful in elucidating the underlying mechanisms of CVDs from physiological and pathological perspectives at DNA, RNA, protein, post-transcriptional, post-translational, and metabolite levels. In this review, we would like to briefly introduce the current single-cell technologies, and will focus on the utilization of single-cell genomics in various heart diseases. Single-cell technologies have great potential in exploration of CVDs, and widespread application of single-cell genomics will promote the understanding and therapeutic treatments for CVDs.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Cefazolin and imipenem enhance AmpC expression and resistance in NagZ-dependent manner in Enterobacter cloacae complex.

BACKGROUND: Enterobacter cloacae complex (ECC) is a common opportunistic pathogen and is responsible for causing various infections in humans. Owing to its inducible chromosomal AmpC ß-lactamase (AmpC), ECC is inherently resistant to the 1st- and 2nd- generation cephalosporins. However, whether ß-lactams antibiotics enhance ECC resistance remains unclear. RESULTS: In this study, we found that subinhibitory concentrations (SICs) of cefazolin (CFZ) and imipenem (IMP) can advance the expression of AmpC and enhance its resistance towards ß-lactams through NagZ in Enterobacter cloacae (EC). Further, AmpC manifested a substantial upregulation in EC in response to SICs of CFZ and IMP. In nagZ knockout EC (ΔnagZ), the resistance to ß-lactam antibiotics was rather weakened and the effect of CFZ and IMP on AmpC induction was completely abrogated. NagZ ectopic expression can rescue the induction effects of CFZ and IMP on AmpC and increase ΔnagZ resistance. More importantly, CFZ and IMP have the potential to induce the expression of AmpR's target genes in a NagZ-dependent manner. CONCLUSIONS: Our findings suggest that NagZ is a critical determinant for CFZ and IMP to promote AmpC expression and resistance and that CFZ and IMP should be used with caution since they may aggravate ECC resistance. At the same time, this study further improves our understanding of resistance mechanisms in ECC.

Genome-wide identification and expression analysis of glutathione S-transferase gene family to reveal their role in cold stress response in cucumber.

The plant glutathione S-transferases (GSTs) are versatile proteins encoded by several genes and play vital roles in responding to various physiological processes. Members of plant GSTs have been identified in several species, but few studies on cucumber (Cucumis sativus L.) have been reported. In this study, we identified 46 GST genes, which were divided into 11 classes. Chromosomal location and genome mapping revealed that cucumber GSTs (CsGSTs) were unevenly distributed in seven chromosomes, and the syntenic regions differed in each chromosome. The conserved motifs and gene structure of CsGSTs were analyzed using MEME and GSDS 2.0 online tools, respectively. Transcriptome and RT-qPCR analysis revealed that most CsGST members responded to cold stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for differentially expressed CsGSTs under cold stress revealed that these genes responded to cold stress probably through "glutathione metabolism." Finally, we screened seven candidates that may be involved in cold stress using Venn analysis, and their promoters were analyzed using PlantCARE and New PLACE tools to predict the factors regulating these genes. Antioxidant enzyme activities were increased under cold stress conditions, which conferred tolerance against cold stress. Our study illustrates the characteristics and functions of CsGST genes, especially in responding to cold stress in cucumber.

Time to Positivity Facilitates an Early Differential Diagnosis of Candida tropicalis from Other Candida species.

Background: Candidemia caused by Candida tropicalis has more serious adverse consequences and an even higher mortality. Time to positivity (TTP) has been widely used to identify microbial species, resistant microorganisms and distinguish real pathogens and pollutants. However, few studies have demonstrated TTP as a presumptive diagnosis of C. tropicalis in patients with candidemia. Patients and Methods: A retrospective study of 136 episodes of candidemia and simulated blood cultures with 314 episodes of confirmed Candida strains were applied to explore the role of TTPs in diagnosing C. tropicalis. TTPs were recorded as the shorter one if both aerobic and anaerobic vials were positive. Lastly, relationships were tested between TTPs and resistance and initial inocula concentration. Results: For the retrospective study, the mean of TTPs for C. tropicalis from 136 patients with candidemia was significantly shorter than other Candida species. The area under the receiver operating characteristics (ROC) curve was 0.8896 ± 0.030 with a sensitivity of 92.86% and a specificity of 77.87%, respectively, indicating TTPs with a cut-off value of <25.50 h had a strong diagnostic power for C. tropicalis in patients with candidemia. Moreover, TTPs from 314 simulated blood cultures showed similar results as the retrospective study, demonstrating TTP is a powerful diagnostic tool in early diagnosing C. tropicalis in patients with candidemia. Additionally, our results showed no statistical significance between TTPs and initial inocula concentration and resistance of Candida species, suggesting initial inocula concentration does not impact TTPs, and TTPs may not be promising in predicting the resistance of all Candida species. Conclusion: TTP can be employed to early distinguish C. tropicalis from other Candida species in patients with candidemia, which is extremely helpful to initiate empiric antifungal treatments to improve clinical outcomes.

Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). METHODS: CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. RESULTS: Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066-7.146; P = 0.036). CONCLUSION: CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.

Prognostic value of plasma adipokine chemerin in patients with coronary artery disease.

Background: Adipokine chemerin was proven to be associated with coronary artery disease (CAD), but its prognostic implications in CAD remain unclear. Methods: This study consists of two parts, one is a basic study and the other is a clinical cohort study. First, we investigated the differential expression of six adipokines in the atherosclerotic mice model compared to mice with milder degrees of atherosclerosis and mice without atherosclerosis using microarray data. We then examined the potential of chemerin as a diagnostic and prognostic indicator in a CAD cohort. A total of 152 patients were enrolled in our study, including 77 patients with angiographically proven CAD and 75 control subjects without cardiovascular disease. Plasma adipokine chemerin levels were measured in all patients, and major adverse cardiovascular events (MACEs) were followed up, including ischemic stroke, non-fatal myocardial infarction, revascularization, and cardiovascular death. Results: In the aortas of atherosclerotic mice, chemerin expression was up-regulated compared to control mice. The plasma chemerin levels of CAD patients were higher than those of non-CAD patients (128.93 ± 37.06 vs. 109.85 ± 27.47 mmol/L, respectively, P < 0.001). High chemerin levels were an independent predictor of CAD (ß = 2.702, 95% CI, 1.344-5.431, P = 0.001). We followed up with patients for a median duration of 5.5 years (3.9-5.6). The Kaplan-Meier curves showed that patients in the high chemerin group had a significantly higher risk of MACEs than the low chemerin group in patients with CAD (log-rank P = 0.003), not with non-CAD (Log-rank P = 0.120). Furthermore, Cox multivariate analysis revealed that high chemerin levels were an independent predictor of MACEs (HR 2.267; 95% CI, 1.139-4.515; P = 0.020). Finally, the cellular study showed that chemerin is predominantly expressed in PBMC-derived macrophages. Conclusion: Plasma chemerin levels were increased in the CAD patients, and a high chemerin level increased the risk of MACEs in CAD patients.

Prognostic impact of coronary microvascular dysfunction assessed by caIMR in overweight with chronic coronary syndrome patients.

Objective: Coronary microvascular dysfunction (CMD) may associate with adverse cardiovascular events in obese patients. Coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed as a less-invasive and pressure-wire-free index to assess CMD. We aimed to investigate the impact of coronary microvascular function assessed by caIMR in patients with overweight and chronic coronary syndrome (CCS). Methods: CCS patients who underwent coronary angiography between 2015 to 2018 were included. Overweight was defined as BMI≥24.0kg/m². Impaired coronary microvascular function was defined as caIMR≥25U. The patients were classified according to BMI and caIMR. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier and Cox regression analyses evaluated the association between caIMR and MACE. Results: Two hundred and eighty-two CCS patients were enrolled. Among these, 169 (59.93%) were overweight. Impaired coronary microvascular function was higher in overweight patients than in patients with normal weight (49.70% vs. 38.05%; P=0.035). During 35 months of follow-up, 33 MACE had occurred. Among the total CCS population, MACE was higher in patients with high caIMR than in low caIMR (18.11% vs. 6.45%, P=0.003). In subgroups analysis, MACE was higher in overweight patients with high caIMR than low caIMR (20.24% vs. 7.06%, P=0.014), while there were no significant differences in normal-weight patients. Multivariate Cox analysis demonstrated that caIMR≥25 was independently associated with MACE in overweight patients (HR, 2.87; 95% CI, 1.12-7.30; P=0.027) but not in the normal-weight patients. In addition, caIMR showed a significant predictive value for adverse outcomes in overweight patients and provided an incremental prediction when added to a prediction model with BMI. Conclusions: Impaired coronary microvascular function assessed by caIMR was common and is an independent predictor of MACE in overweight patients with CCS.