Analysis of differential metabolites in serum metabolomics of patients with aortic dissection.

BACKGROUND: Pathogenesis and diagnostic biomarkers of aortic dissection (AD) can be categorized through the analysis of differential metabolites in serum. Analysis of differential metabolites in serum provides new methods for exploring the early diagnosis and treatment of aortic dissection. OBJECTIVES: This study examined affected metabolic pathways to assess the diagnostic value of metabolomics biomarkers in clients with AD. METHOD: The serum from 30 patients with AD and 30 healthy people was collected. The most diagnostic metabolite markers were determined using metabolomic analysis and related metabolic pathways were explored. RESULTS: In total, 71 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism and four different metabolites considered of most diagnostic value including N2-gamma-glutamylglutamine, PC(phocholines) (20:4(5Z,8Z,11Z,14Z)/15:0), propionyl carnitine, and taurine. These four predictive metabolic biomarkers accurately classified AD patient and healthy control (HC) samples with an area under the curve (AUC) of 0.9875. Based on the value of the four different metabolites, a formula was created to calculate the risk of aortic dissection. Risk score = (N2-gamma-glutamylglutamine × -0.684) + (PC (20:4(5Z,8Z,11Z,14Z)/15:0) × 0.427) + (propionyl carnitine × 0.523) + (taurine × -1.242). An additional metabolic pathways model related to aortic dissection was explored. CONCLUSION: Metabolomics can assist in investigating the metabolic disorders associated with AD and facilitate a more in-depth search for potential metabolic biomarkers.

Development and validation of a risk prediction model for valve regurgitation in Behçet's disease.

BACKGROUND: In Behçet's disease (BD), mild-to-severe valvular regurgitation (VR) poses a serious complication that contributes significantly to heart failure and eventually death. The accurate prediction of VR is crucial in the early stages of BD subjects for improved prognosis. Accordingly, this study aimed to develop a nomogram that can detect VR early in the course of BD. METHODS: One hundred seventy-two patients diagnosed with Behçet's disease (BD) were conducted to assess cardiac valve regurgitation as the primary outcome. The severity of regurgitation was classified as mild, moderate, or severe. The parameters related to the diagnostic criteria were used to develop model 1. The combination of stepAIC, best subset, and random forest approaches was employed to identify the independent predictors of VR and thus establish model 2 and create a nomogram for predicting the probability of VR in BD. Receiver operating characteristics (ROC) and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Thirty-four patients experienced mild-to-severe VR events. Model 2 was established using five variables, including arterial involvement, sex, age at hospitalization, mean arterial pressure, and skin lesions. In comparison with model 1 (0.635, 95% CI: 0.512-0.757), the ROC of model 2 (0.879, 95% CI: 0.793-0.966) was improved significantly. DCA suggested that model 2 was more feasible and clinically applicable than model 1. CONCLUSION: A predictive model and a nomogram for predicting the VR of patients with Behçet's disease were developed. The good performance of this model can help us identify potential high-risk groups for heart failure. Key Points • In this study, the predictors of VR in BD were evaluated, and a risk prediction model was developed for the early prediction of the occurrence of VR in patients with BD. • The VR prediction model included the following indexes: arterial involvement, sex, age at hospitalization, mean arterial pressure, and skin lesions. • The risk model that we developed was better and more optimized than the models built with diagnostic criteria parameters, and visualizing and personalizing the model, a nomogram, provided clinicians with an easy and intuitive tool for practical prediction.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Targeting estrogen receptor signaling for treating heart failure.

Heart failure (HF) is a significant public health problem worldwide. It has long been noted that premenopausal women, compared to postmenopausal women and men, have lower rates for developing this disease, as well as subsequent morbidity and mortality. This difference has been attributed to estrogen playing a cardioprotective role in these women, though exactly how it does so remains unclear. In this review, we examine the presence of estrogen receptors within the cardiovascular system, as well as the role they play behind the cardioprotective effect attributed to estrogen. Furthermore, we highlight the underlying mechanisms behind their alleviation of HF, as well as possible treatment approaches, such as hormone replacement therapy and exercise regimens, to manipulate these mechanisms in treating and preventing HF.

4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes.

A high-fat diet (HFD) plays a critical role in hepatocyte insulin resistance. Numerous models and factors have been proposed to elucidate the mechanism of palmitic acid (PA)-induced insulin resistance. However, proteomic studies of insulin resistance by HFD stimulation are usually performed under insulin conditions, leading to an unclear understanding of how a HFD alone affects hepatocytes. Here, we mapped the phosphorylation rewiring events in PA-stimulated HepG2 cells and found PA decreased the phosphorylation level of the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2) at S65/T70. Further experiments identified 4EBP2 as a key node of insulin resistance in either HFD mice or PA-treated cells. Reduced 4EBP2 levels increased glucose uptake and insulin sensitivity, whereas the 4EBP2_S65A/T70A mutation exacerbated PA-induced insulin resistance. Additionally, the nascent proteome revealed many glycolysis-related proteins translationally regulated by 4EBP2 such as hexokinase-2, pyruvate kinase PKM, TBC1 domain family member 4, and glucose-6-phosphate 1-dehydrogenase. In summary, we report the critical role of 4EBP2 in regulating HFD-stimulated insulin resistance in hepatocytes.

ANGPTL2 aggravates LPS-induced septic cardiomyopathy via NLRP3-mediated inflammasome in a DUSP1-dependent pathway.

Angiopoietin-like protein 2 (ANGPTL2) was implicated in various cardiovascular diseases; however, its role in lipopolysaccharide (LPS)-related septic cardiomyopathy remains unclear. Herein, mice were exposed to LPS to generate septic cardiomyopathy, and adeno-associated viral vector was employed to overexpress ANGPTL2 in the myocardium. Besides, mice were treated with adenoviral vector to knock down ANGPTL2 in hearts. ANGPTL2 expressions in hearts and cardiomyocytes were upregulated by LPS challenge. ANGPTL2 overexpression aggravated, while ANGPTL2 silence ameliorated LPS-associated cardiac impairment and inflammation. Mechanically, we found that ANGPTL2 activated NLRP3 inflammasome via suppressing DUSP1 signaling, and NLRP3 knockdown abrogated the detrimental role of ANGPTL2 in aggravating LPS-induced cardiac inflammation. Furthermore, DUSP1 overexpression significantly inhibited ANGPTL2-mediated NLRP3 activation, and subsequently improved LPS-related cardiac dysfunction. In summary, ANGPTL2 exacerbated septic cardiomyopathy via activating NLRP3-mediated inflammation in a DUSP1-dependent manner, and our study uncovered a promising therapeutic target in preventing septic cardiomyopathy.

PET117 assembly factor stabilizes translation activator TACO1 thereby upregulates mitochondria-encoded cytochrome C oxidase 1 synthesis.

Cytochrome c oxidase, also known as complex IV, facilitates the transfer of electrons from cytochrome c to molecular oxygen, resulting in the production of ATP. The assembly of complex IV is a tightly regulated and intricate process that entails the coordinated synthesis and integration of subunits encoded by the mitochondria and nucleus into a functional complex. Accurate regulation of translation is crucial for maintaining proper mitochondrial function, and defects in this process can lead to a wide range of mitochondrial disorders and diseases. However, the mechanisms governing mRNA translation by mitoribosomes in mammals remain largely unknown. In this study, we elucidate the critical role of PET117, a chaperone protein involved in complex IV assembly, in the regulation of mitochondria-encoded cytochrome c oxidase 1 (COX1) protein synthesis in human cells. Depletion of PET117 reduced mitochondrial oxygen consumption rate and impaired mitochondrial function. PET117 was found to interact with and stabilize translational activator of COX1 (TACO1) and prevent its ubiquitination. TACO1 overexpression rescued the inhibitory effects on mitochondria caused by PET117 deficiency. These findings provide evidence for a novel PET117-TACO1 axis in the regulation of mitochondrial protein expression, and revealed a previously unknown role of PET117 in human cells.

Dynamic adjustable metalens based on a stretchable substrate with a double-layer metal microstructure.

Based on the impedance-matching theory, a double-layer metal structure dynamical focusing cylindrical metalens with a stretchable substrate was designed at the operation frequency of 0.1 THz. The diameter, initial focal length, and NA of the metalens were 80 mm, 40 mm, and 0.7, respectively. The transmission phase of the unit cell structures could cover 0-2π by changing the size of the metal bars, and then the different unit cells were spatially arranged as the designed phase profile for the metalens. When the stretching range of the substrate was about 100%-140%, the focal length changed from 39.3 mm to 85.5 mm, the dynamic focusing range was about 117.6% of the minimum focal length, and the focusing efficiency decreases from 49.2% to 27.9%. Then, by rearranging the unit cell structures, a dynamically adjustable bifocal metalens was numerically realized. Using the same stretching ratio, compared to a single focus metalens, the bifocal metalens can provide a larger focal length control range.

Mapping the Protein Kinome: Current Strategy and Future Direction.

The kinome includes over 500 different protein kinases, which form an integrated kinase network that regulates cellular phosphorylation signals. The kinome plays a central role in almost every cellular process and has strong linkages with many diseases. Thus, the evaluation of the cellular kinome in the physiological environment is essential to understand biological processes, disease development, and to target therapy. Currently, a number of strategies for kinome analysis have been developed, which are based on monitoring the phosphorylation of kinases or substrates. They have enabled researchers to tackle increasingly complex biological problems and pathological processes, and have promoted the development of kinase inhibitors. Additionally, with the increasing interest in how kinases participate in biological processes at spatial scales, it has become urgent to develop tools to estimate spatial kinome activity. With multidisciplinary efforts, a growing number of novel approaches have the potential to be applied to spatial kinome analysis. In this paper, we review the widely used methods used for kinome analysis and the challenges encountered in their applications. Meanwhile, potential approaches that may be of benefit to spatial kinome study are explored.

Complete genome sequence analysis and biological characteristics of Newcastle disease viruses from different hosts in China.

Newcastle disease (ND) is one of the most serious diseases affecting poultry worldwide. In 2022, we studied two strains of Newcastle disease virus (NDV) from pigeons and magpies identified by PCR and propagated in SPF chicken embryos. The whole genome of the virus was then expanded and its biological characteristics were studied. The results showed that NDV was isolated from pigeons and magpies. Virus present in the allantoic fluid could agglutinate red blood cells and could not be neutralized by serum positive for avian influenza. Sequencing showed that the gene length of the two isolates was 15,191 bp, had high homology and was located in the same branch of the phylogenetic tree, both belonging to genotype VI.1.1. The sequence of 112-117 amino acids in the F gene sequence was 112R-R-Q-K-R-F117, which constituted virulent strain characteristics. The HN gene contained 577 amino acids, which is also consistent with the characteristics of a virulent strain. The results from the study of biological characteristics revealed that the virulence of SX/TY/Pi01/22 was slightly stronger. There were only four different bases in the complete sequence of the two strains. Comprehensive analysis revealed that the G at 11,847 site of the SX/TY/Ma01/22 strain may change to T, leading to translation of amino acids from R to S, thereby weakening viral virulence. Therefore, NDV was transmitted from pigeons to magpies, indicating that the pathogen could be transmitted between poultry and wild birds.

Clinical characteristics and predictors for cardiovascular system involvement in patients with Behçet's disease.

OBJECTIVES: The purpose of this study is to analyse the clinical characteristics of Behçet's disease (BD) patients in China with or without cardiovascular system involvement, and to develop a risk model to identify factors related to cardiovascular involvement in BD. METHODS: This retrospective cohort study, using the information on BD in Shenzhen People's Hospital from January 2000 to December 2021, included 95 patients: BD patients without cardiovascular system involvement (n=63) and with cardiovascular system involvement (n=32). RESULTS: Patients with BD who were males and had a combination of hypertension and a longer duration of disease were more likely to have cardiovascular involvement (p < 0.05). Compared to patients without cardiovascular involvement, manifestations of genital ulcers are rarely observed in those with cardiovascular involvement (60.32% vs. 37.50%, p=0.035). The binary logistic regression analysis found that ascending aortic widening and a history of hypertension were independent risk factors for BD with cardiovascular system involvement (OR=1.277, 95% CI 1.09, 1.495, p=0.002; OR=11.578, 95% CI 1.308, 102.639, p=0.028). The established prediction model indicated that can help to predict the likelihood of cardiovascular involvement in a patient with BD. CONCLUSIONS: Cardiovascular involvement in BD is not at all rare, however, it is often underreported due to a lack of specificity. BD patients who are male, have a history of combined hypertension, and have a long duration of disease should be focused on the presence of combined cardiovascular system involvement, with particular attention to the patient's ascending aortic internal diameter.

Systematic Insight of Resveratrol Activated SIRT1 Interactome through Proximity Labeling Strategy.

SIRT1 functions by regulating the modification of proteins or interacting with other proteins to form complexes. It has been widely studied and found to play significant roles in various biological processes and diseases. However, systematic studies on activated-SIRT1 interactions remain limited. Here, we present a comprehensive SIRT1 interactome under resveratrol stimulation through proximity labeling methods. Our results demonstrated that RanGap1 interacted with SIRT1 in HEK 293T cells and MCF-7 cells. SIRT1 regulated the protein level of RanGap1 and had no obvious effect on RanGap1 transcription. Moreover, the overexpression of Rangap1 increased the ROS level in MCF-7 cells, which sensitized cells to resveratrol and reduced the cell viability. These findings provide evidence that RanGap1 interacts with SIRT1 and influences intracellular ROS, critical signals for mitochondrial functions, cell proliferation and transcription. Additionally, we identified that the SIRT1-RanGap1 interaction affects downstream signals induced by ROS. Overall, our study provides an essential resource for future studies on the interactions of resveratrol-activated SIRT1. There are conflicts about the relationship between resveratrol and ROS in previous reports. However, our data identified the impact of the resveratrol-SIRT1-RanGap1 axis on intracellular ROS.

Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation.

Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow's direction on the blood vessel's luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator.

Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF. METHODS: Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis. RESULTS: Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 - 0.96), OR = 0.73, (95%CI 0.61 - 0.86), and OR = 0.74, (95%CI 0.66 - 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 - 0.83)]. CONCLUSIONS: No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.

Proteomic and Phosphoproteomic Analyses Reveal the Oncogenic Role of PTK7-NDRG1 Axis in Non-small-cell Lung Cancer Cell Resistance to AZD9291.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the most important chemotherapeutics for non-small-cell lung cancer (NSCLC) therapy. The resistance to EGFR-TKIs is one of the biggest obstacles to NSCLC outcome. In this study, taking advantage of phospho- and proximal proteomic techniques, we analyzed the network rearrangement in cell lines responding to AZD9291 treatment and found that cell-cell adhesion was dramatically enhanced in AZD9291-resistant cells. Further analysis revealed that protein tyrosine kinase 7 (PTK7) expression was significantly elevated. Knockdown or overexpression assays showed that PTK7 played a critical role in improving cell adhesion, which enhanced drug resistance. Because PTK7 is a membrane-localized pseudokinase, the proximal labeling probe BirA* was fused to reveal PTK7-interacting proteins. We found that PTK7 interacted with and stabilized NDRG1, which is located predominantly adjacent to adherens junctions. Downregulation of PTK7 or NDRG1 eliminated the resistance of H1975-resistant (H1975-R) and PC9-resistant (PC9-R) cells to AZD9291, suggesting that the PTK7-NDRG1 axis might be a potential target to eliminate the EGFR-TKI resistance during NSCLC therapy.

Retrograde recanalization of radial artery occlusion via the distal transradial artery: A single-center experience.

Background: Radial artery occlusion (RAO) often occurs after catheterization when using a transradial artery approach. Objective: This prospective study assessed the success and feasibility of accessing the distal transradial artery (dTRA) for retrograde recanalization of RAO. Methods: From June 2019 to December 2021, 44 consecutive patients who had undergone cardiac catheterization resulting in RAO were given retrograde recanalization via the dTRA. According to the result of the procedure (primary endpoint), patients' cases were analyzed as successful or failed. Rates of post-operative patency and adverse events were calculated up to 12 months. Results: The procedural success rate was 88.6%. Compared with the successful group, a significantly higher percentage of patients in the failed group were current smokers and/or suffered from diabetes mellitus (each, 80.0% cf. 33.3%, P = 0.046); had undergone at least 3 previous cardiac catheterizations (60.0% cf. 12.8%, P = 0.011), lower rate of anticoagulation (30.77% cf. 0%, P = 0.048) and exhibited chronic total occlusion (100.0% cf. 51.28%, P = 0.041). In each group, one patient each had minor bleeding at the access site and hematoma. The patency rates in the successful group at postoperative 3, 6, and 12 months were 48.7, 43.6, and 35.9%, respectively. Conclusion: The dTRA approach for retrograde recanalization of RAO showed a high procedural success rate, but with patency rates of <50% at follow-up.

Comparative efficacy and safety of antiplatelet or anticoagulant therapy in patients with chronic coronary syndromes after percutaneous coronary intervention: A network meta-analysis of randomized controlled trials.

Aimed to evaluate and compare the interactive effects of different antiplatelet or anticoagulation strategies in patients with chronic coronary syndromes (CCS) after percutaneous coronary intervention (PCI). Randomized controlled trials comparing different antiplatelet or anticoagulant strategies in patients with CCS after PCI were included. The primary outcomes were major adverse cardiovascular event (MACE), mortality, ischemic and bleeding events. Compared to aspirin alone, addition of prasugrel or ticagrelor to aspirin resulted in lower risk of myocardial infarction (MI) [odds ratio (OR): 0.38 (95% confidence interval 0.38-0.62); 0.810-0.84 (0.69-0.98)] and any stroke [0.56 (0.42-0.75)] at the expense of increased risk of major bleeding [1.79 (1.34-2.39); 2.08-2.38 (1.56-3.28)], whereas, clopidogrel monotherapy reduced the risk of any stroke, major bleeding, and intracranial bleeding. On subgroup analysis, compared with aspirin alone, addition of prasugrel resulted in lower MACE [0.72 (0.60-0.86)], MI [0.48 (0.38-0.62)], and stent thrombosis [0.29 (0.09-0.91)], whereas, addition of rivaroxaban 2.5 mg resulted in lower risk of MACE [0.72 (0.60-0.87)], cardiac death [0.71 (0.52-0.98)] and any stroke [0.65 (0.45-0.95)], but not reduced MI. Both prasugrel and rivaroxaban 2.5 mg increased major bleeding [1.79 (1.34-2.39); 1.72 (1.33-2.22)]. Clopidogrel monotherapy was associated with lower MACE [0.72 (0.58-0.90)], any stroke [0.42 (0.24-0.73)], and major bleeding [0.62 (0.40-0.96)]. Adding prasugrel or ticagrelor led to a reduced incidence of MI and prasugrel was also found to reduce the risk of MACE and stent thrombosis in CCS patients with low risk of bleeding after PCI. Clopidogrel monotherapy has advantage in reducing MACE, stroke, and major bleeding events in CCS patients at high risk of bleeding after PCI. Systematic Review Registration: https://clinicaltrials.gov/, PROSPERO Identifier: CRD 42021291050.

ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway.

Angiopoietin-like protein 2 (ANGPTL2) plays versatile roles in various cardiovascular diseases. Its connection to doxorubicin (DOX)-related cardiomyopathy, however, remains elusive. To determine the role of ANGPTL2, an adeno-associated viral vector was used to overexpress ANGPTL2 in the murine heart 4 weeks before DOX treatment (15 mg/kg). Moreover, mice were injected with adenoviral vectors to knock down ANGPTL2 in the myocardium. Echocardiography and hemodynamics were used to determine the cardiac function. The effect of ANGPTL2 and its downstream target were elucidated by applying molecular and biochemical strategies. We found that ANGPTL2 expression was significantly increased in response to DOX stimulation. Moreover, cardiac-specific ANGPTL2 overexpression exacerbated DOX-related cardiac dysfunction, myocardial apoptosis, and oxidative stress. Mechanistically, ANGPTL2 aggravated DOX-induced cardiac injury via inhibiting the dual specificity phosphatase 1 (DUSP1) pathway and DUSP1 overexpression significantly impeded DOX-induced cardiomyopathy in ANGPTL2-overexpressed mice. Altogether, ANGPTL2 aggravated DOX-related cardiac injury by suppressing the DUSP1 pathway.