Abstract Background Cardiac macrophages (cMacs) have been implicated in myocardial repair following myocardial infarction (MI), yet their therapeutic potential in ischaemic cardiomyopathy (ICM) remains limited by an incomplete understanding of their molecular regulation. Cluster of Differentiation 163 (CD163) is highly expressed in these macrophages, yet its functional role in regulating post‐MI cardiac repair remains unknown. Methods A cross‐sectional clinical study was conducted to assess the association between circulating soluble CD163 concentration and heart failure due to ICM. To investigate the functional contribution of CD163 in ICM, wild‐type (WT) and Cd163−/− mice were subjected to permanent ligation of the left anterior descending coronary artery. Single‐cell RNA sequencing was employed to analyse transcriptional changes in cardiac immune cells. Recombinant osteopontin (OPN) and CD163 were administered to assess their therapeutic effect in Cd163−/− mice. Results Circulating soluble CD163 levels were markedly elevated in patients with ICM‐induced heart failure compared with individuals without heart failure (median difference 34.5 ng/mL, IQR 13.6–54.6 ng/mL, p = .002) and showed a positive correlation with the extent of systolic dysfunction and left ventricular (LV) dilation. Cd163−/− mice displayed aggravated LV systolic dysfunction, reduced ejection fraction and fractional shortening, impaired myocardial strain and reduced relative wall thickness post‐MI. Recombinant CD163 protein could reverse systolic dysfunction and LV dilation in Cd163−/− mice after MI. CD163 was predominantly expressed in CCR2− resident cMacs, and CD163 deficiency altered transcriptional programmes of macrophages without affecting their polarization status, with enrichment in cytokine signalling and extracellular matrix‐related pathways. Spp1 (OPN) expression was significantly downregulated in Cd163−/− hearts under both sham and MI conditions. Administration of recombinant OPN improved systolic function, reduced ventricular dilation, decreased fibrotic scar size and restored the elastin‐to‐collagen ratio in Cd163−/− mice. Conclusions In cMacs, CD163 contributes to post‐MI repair by upregulating OPN expression, which in turn helps maintain systolic function. Key points Soluble CD163 is elevated in ICM and correlates with LV dysfunction. Cd163−/− mice show worsened post‐MI systolic dysfunction and dilation. Recombinant CD163 reverses dysfunction in Cd163−/− mice. OPN restores function and improves LV structure in Cd163−/− mice.

Importance:The optimal timing and approach for initiating cardiac rehabilitation (CR) in critically ill patients during the acute phase of acute decompensated heart failure (ADHF) remains uncertain. Objective:To evaluate the effects of CR on physical function and rehospitalization for critically ill patients with ADHF admitted to the cardiac intensive care unit (CICU). Design, Setting, and Participants:In this single-center, single-blind randomized clinical trial conducted in China, critically ill patients with severe ADHF admitted to the CICU were recruited between March 26, 2021, and September 1, 2022. All patients were followed up for 6 months, and investigators were blinded to the group assignment. Interventions:After short-term therapy, participants were randomized 1:1 to an early progressive and personalized CR program for patients with ADHF (AHF-CR program) that was administered exclusively during the patients' CICU stay or to usual care. Main Outcomes and Measures:The primary outcomes were Short Physical Performance Battery (SPPB) score at hospital discharge and 6-month all-cause rehospitalization rates. These outcomes were analyzed using an intention-to-treat approach including all patients after randomization. The Perme Intensive Care Unit Mobility (PERME) score was incorporated as an exploratory outcome during analysis to assess mobility status in critically ill patients. Results:This study included 120 patients (mean [SD] age, 68.6 [12.3] years; 80 [66.7%] male). At randomization, pulmonary crackles were observed in 49 patients in the control group (81.7%) and 43 patients in the intervention group (71.7%). Additionally, 62 patients (51.7%) had an arterial partial pressure of oxygen to fraction of inspired oxygen ratio below 300 mm Hg. A total of 40 patients (33.3%) received intravenous vasoactive medications, and 87 (72.5%) received intravenous loop diuretics. The median difference in SPPB scores between groups was 1.0 (95% CI, 0-2.0; P = .16), which was not significant. Six-month rehospitalization rates were comparable between the control and intervention groups (16 [26.6%] vs 17 [28.3%]; hazard ratio, 1.00 [95% CI, 0.51-1.99]; P = .99). Exploratory analysis revealed that the intervention group had higher PERME scores, with a median between-group difference of 2.76 (95% CI, 0.77-4.74; adjusted P = .04). Conclusions and Relevance:In this randomized clinical trial of critically ill patients with ADHF, the AHF-CR program did not significantly improve SPPB scores or rehospitalization rates. However, it may offer potential physical benefits, including enhanced mobility. Trial Registration:Chinese Clinical Trial Registry Identifier: ChiCTR2100050151.

Rationale: Adipose tissue buffers dietary lipids to maintain postprandial lipid homeostasis. Adipose tissue macrophages (ATMs) mediate the phagocytosis of postprandial lipids from the exogenous diet, generating high-density lipoprotein (HDL) particles that facilitate lipid circulation and excretion. However, the underlying mechanisms remain poorly understood. This study investigates the effects of esculetin, a coumarin compound, on postprandial cholesterol circulation and excretion following a high-fat meal. Methods: Mice were fed a lipid-rich meal for three days to assess the effects of esculetin on postprandial lipid circulation, using serum lipid profiling and metabolomics analysis. Epididymal white adipose tissue (eWAT) removal and flow cytometry were performed to analyze ATMs and confirm their role in mediating esculetin's effects on postprandial lipemia. Epigenetic profiling, transcriptome analysis, chromatin immunoprecipitation, and Terahertz chemical microscopy were employed to elucidate the molecular targets and mechanisms of esculetin. Results: Esculetin significantly elevates postprandial HDL cholesterol levels to values comparable to pitavastatin and modifies serum metabolites involved in bile-mediated cholesterol excretion, leading to increased bile acid concentrations in the bile. This effect is mediated by an increased ratio and phagocytic activity of a subset of ATMs expressing the scavenger receptor CD36, as eWAT removal and CD36 blockade inhibit this response. Furthermore, esculetin enhances the uptake of oxidized LDL via CD36, as demonstrated in cultured macrophages, and induces epigenetic changes controlled by the key transcription factor C/EBPβ, accompanied by increased C/EBPβ binding to the Cd36 promoter. A direct interaction between esculetin and C/EBPβ was observed using Terahertz chemical microscopy. Additionally, the activation of C/EBPβ by esculetin in ATMs was confirmed in vivo. Conclusion: Esculetin accelerates postprandial lipid circulation by binding to C/EBPβ and enhancing CD36-dependent phagocytosis in ATMs.

Aim:To evaluate the achievement of metabolic risk factor targets and influencing factors in ACS patients with diabetes during the 12 months after discharge. Methods:We retrospectively analyzed data from the Chinese Cardiovascular Association database-iHeart Project. Patients who were hospitalized with a diagnosis of ACS between 2014 and 2021 and who had at least one measurement record of LDL-C, BP, or HbA1c within 12 months after discharge were included. We further stratified patients by diabetes status and analyzed the correlation between clinical characteristics, measurement strategy, and achievement of targets. Results:Diabetes was identified in 1,027 (27.5%) of the eligible patients. The proportions of patients with diabetes achieving targets of LDL-C, BP, and HbA1c levels were 42.4%, 61.5%, and 43.7%, respectively. However, combined achievement rate was significantly lower in patients with diabetes than patients without diabetes (16.6% vs. 26.6%). Patients with diabetes who underwent the first measurement within three months or had ≥3 measurements within 12 months were positively associated with achieving combined targets. Conclusions:The achievement of multifactorial targets among patients with ACS is suboptimal, particularly among patients with concomitant diabetes. The optimal measurement strategy post-discharge is essential for improving the comprehensive management of metabolic risk factors in ACS patients.

Older adults with established cardiovascular diseases (CVD) are at elevated risk of heart failure (HF). Frailty, a hallmark of multi-system aging, may contribute to HF development through inflammation. However, population-based evidence remains scarce. Leveraging data from 49,530 CVD patients in the UK Biobank, frailty was measured by five components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. We employed Cox regression models to assess the association between frailty and incident HF, and conducted mediation analyses to evaluate mediating roles of 15 inflammatory markers in this association. Furthermore, we constructed a polygenic risk score (PRS) for HF risk based on the Global Biobank Meta-analysis Initiative (N = 1,020,441), and evaluated the joint association and interaction between frailty and PRS in relation to incident HF. During a median follow-up of 13.3 years, 6293 participants developed HF. Compared to robust individuals, pre-frail (hazard ratio (HR) = 1.31 [95

Macrophage depletion exacerbates pressure overload-induced heart failure, but therapeutic translation is hindered by macrophage subset heterogeneity. The functional role of CD163+ macrophages in heart failure remains unclear. Transverse aortic constriction (TAC) was employed to induce pressure overload. Cd163−/− mice exhibited significantly aggravated TAC-induced left ventricular systolic dysfunction, as demonstrated by reduced ejection fraction, fractional shortening, and global longitudinal strain, compared to wild-type (WT) controls. RNA sequencing of cardiac tissues revealed significant differential gene expression between TAC-treated WT and Cd163−/− mice, especially in pathways governing mitochondrial bioenergetics and homeostasis. Transmission electron microscopy confirmed greater accumulation of dysfunctional mitochondria in cardiomyocytes of Cd163−/− mice relative to WT following TAC. Additionally, the proportion of CD163+ macrophages among cardiac macrophages increased post-TAC. Serum IL-10 levels and cardiac macrophage IL-10 expression were significantly diminished in Cd163−/− mice compared to WT after TAC. IL-10 supplementation effectively reversed the TAC-induced impairment in left ventricular systolic function in both WT and Cd163−/− mice, and reduced NADH/NAD+ ratios, reduced mitochondrial dysfunction, and improved mitochondrial membrane potential in Cd163−/− mice. Cross-sectional clinical data supported these findings, showing decreased IL-10 levels as a significant risk factor for heart failure in hypertensive patients (odds ratio: 0.397; 95

The optimal timing and approach for initiating cardiac rehabilitation (CR) in critically ill patients during the acute phase of acute decompensated heart failure (ADHF) remains uncertain. To evaluate the effects of CR on physical function and rehospitalization for critically ill patients with ADHF admitted to the cardiac intensive care unit (CICU). In this single-center, single-blind randomized clinical trial conducted in China, critically ill patients with severe ADHF admitted to the CICU were recruited between March 26, 2021, and September 1, 2022. All patients were followed up for 6 months, and investigators were blinded to the group assignment. After short-term therapy, participants were randomized 1:1 to an early progressive and personalized CR program for patients with ADHF (AHF-CR program) that was administered exclusively during the patients’ CICU stay or to usual care. The primary outcomes were Short Physical Performance Battery (SPPB) score at hospital discharge and 6-month all-cause rehospitalization rates. These outcomes were analyzed using an intention-to-treat approach including all patients after randomization. The Perme Intensive Care Unit Mobility (PERME) score was incorporated as an exploratory outcome during analysis to assess mobility status in critically ill patients. This study included 120 patients (mean [SD] age, 68.6 [12.3] years; 80 [66.7%] male). At randomization, pulmonary crackles were observed in 49 patients in the control group (81.7%) and 43 patients in the intervention group (71.7%). Additionally, 62 patients (51.7%) had an arterial partial pressure of oxygen to fraction of inspired oxygen ratio below 300 mm Hg. A total of 40 patients (33.3%) received intravenous vasoactive medications, and 87 (72.5%) received intravenous loop diuretics. The median difference in SPPB scores between groups was 1.0 (95% CI, 0-2.0; P = .16), which was not significant. Six-month rehospitalization rates were comparable between the control and intervention groups (16 [26.6%] vs 17 [28.3%]; hazard ratio, 1.00 [95% CI, 0.51-1.99]; P = .99). Exploratory analysis revealed that the intervention group had higher PERME scores, with a median between-group difference of 2.76 (95% CI, 0.77-4.74; adjusted P = .04). In this randomized clinical trial of critically ill patients with ADHF, the AHF-CR program did not significantly improve SPPB scores or rehospitalization rates. However, it may offer potential physical benefits, including enhanced mobility. Chinese Clinical Trial Registry Identifier: ChiCTR2100050151

Ventricular aneurysm is a serious complication following myocardial infarction. Increasing evidence suggests that exercise-based cardiac rehabilitation plays a protective role in cardiovascular disease. However, the effects of exercise on ventricular aneurysm and the underlying mechanisms remain poorly understood. Therefore, this study aimed to establish a murine model of ventricular aneurysm and investigate the impact of exercise on this condition, along with its potential mechanisms. In this study, using proximal coronary artery ligation, a murine cardiac ventricular aneurysm model was established and evaluated by real-time myocardial contrast echocardiography. Wild-type male C57BL/6 mice with ventricular aneurysms were randomly assigned to three groups: a Sedentary group (no exercise, n = 7), a moderate-intensity exercise group (5 m/min adaptive exercise for 2 weeks, followed by 12-m/min moderate-intensity exercise for 8 weeks, n = 9), and a high-intensity exercise group (5-m/min adaptive exercise for 2 weeks, followed by 18-m/min high-intensity exercise for 8 weeks, n = 7). After 8 weeks of exercise intervention, moderate-intensity exercise was found to significantly enhance cardiac function, reduce myocardial fibrosis, and inhibit fibroblast activation. In contrast, high-intensity exercise resulted in deteriorated cardiac function and aggravated cardiac injury. Mechanistically, this paradoxical effect was linked to the regulation of PTEN stability and subsequent modulation of Smad2/3 signaling pathway. This study provides a theoretical foundation for the role of exercise in managing ventricular aneurysms and offers insights into optimal exercise intensity levels.

AIMS:Heterozygous familial hypercholesterolaemia (HeFH) is a genetic disorder, characterized by high plasma concentrations of low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the efficacy and safety of recaticimab, a new humanized anti-PCSK9 antibody capable of reducing LDL-C levels in patients with poorly controlled HeFH. METHODS AND RESULTS:REMAIN-3 was a multicentre, randomized, double-blind, placebo-controlled Phase 3 study done at 25 sites in China. Patients with a genetic or clinical diagnosis of HeFH, who were on stable lipid-lowering therapy for ≥28 days, had fasting LDL-C ≥ 2.6 mmol/L (or ≥1.8 mmol/L for those with a history of atherosclerotic cardiovascular disease), and had fasting triglyceride ≤5.6 mmol/L, were randomly allocated in a 2:1 ratio to receive subcutaneous recaticimab at 150 mg or matching placebo every 4 weeks for 12 weeks. The primary endpoint was the percentage change in LDL-C from baseline to Week 12. Overall, 143 patients underwent randomization and received recaticimab (n = 95) or placebo (n = 48). At Week 12, the mean percentage change in LDL-C from baseline was -54.4% (95% CI, -57.9 to -50.8%) in the recaticimab group and -4.5% (95% CI, -9.4 to 0.3%) in the placebo group, with a treatment difference of -49.8% (95% CI, -55.8 to -43.9%; P < 0.0001). Recaticimab was superior to placebo in improving other lipid variables, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein a. Treatment-related adverse events (TRAEs) were comparable between groups (27.4% with recaticimab vs. 25.0% with placebo). The most common TRAEs occurring more frequently with recaticimab than placebo were injection site reaction (8.4% vs. 0%) and increased blood creatine phosphokinase (5.3% vs. 2.1%). CONCLUSION:Recaticimab significantly lowered the LDL-C level compared with placebo, with an acceptable safety profile, providing a new effective treatment option for patients with inadequately controlled HeFH. REGISTRATION:ClinicalTrials.gov Identifier: NCT04844125.

Conventional thrombolytic agents demonstrated limited efficacy in treating thrombotic disorders characterized by narrow therapeutic windows and progressive vascular injury, lacking the required precision, timeliness, and treatment durability. Here an engineered probiotic powered micro-rod robot for targeted and penetrative treatment for thrombus is developed. This micro-rod robot (SrEcNPL) using natural probiotics as bio-carriers, functionalized with thrombolytic carbon nanotubes and platelet membrane-coated nanoparticles loaded with targeted vasodilators. The robot exploits the rapid movement of probiotics, combined with the active targeting ability of the platelet membrane, to achieve rapid and precise drug delivery to thrombus tissue. Based on the natural rod-shaped structure of probiotics, SrEcNPL can deeply penetrate thrombus tissue, achieving faster thrombolysis efficiency. The thrombolytic micro-robot combines thrombus-targeting capability with prolonged circulation time and controlled vasodilation, maintaining vascular patency and inhibiting secondary thrombus. Results indicate that this micro-robot can quickly and accurately target and penetrate thrombus tissue, extending the biological half-life of thrombolytic drugs by ≈332 times and enabling sustained thrombolysis. This novel dual-pronged combined thrombolytic therapy has significant scientific implications for treating thrombotic diseases with narrow therapeutic windows caused by vascular injury.

Diabetes is widely acknowledged as a significant risk factor for atherosclerosis, facilitating plaque formation through various mechanisms. Although both conditions are linked to the aging process, the relationship among cellular senescence, diabetes, and atherosclerosis remains inadequately understood. This study presents evidence that elevated glucose levels expedite the progression of atherosclerosis by promoting macrophage senescence. Increased glucose levels are shown to induce senescence in macrophages, which enhances the uptake of oxidized low-density lipoprotein (ox-LDL) and facilitates the formation of foam cells. This mechanism is driven by lactate production via glycolysis, which activates the lactate receptor GPR132, thereby promoting macrophage senescence. The activation of GPR132 is implicated in mediating senescence and lipid uptake through Src phosphorylation. The deletion of GPR132 markedly reduces macrophage senescence and atherosclerosis in mouse models. Furthermore, saracatinib, a specific Src inhibitor, has been demonstrated to effectively alleviate diabetic atherosclerosis in experimental settings. In clinical samples, elevated plasma lactate levels and the activation of the GPR132-Src pathway in peripheral blood mononuclear cells (PBMCs) are positively associated with coronary stenosis. These findings propose a potential mechanism through which diabetes accelerates atherosclerosis via the lactate-GPR132-Src pathway, underscoring macrophage senescence as a pivotal target in the context of diabetic atherosclerosis.

Introduction Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI. Objectives This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI. Methods We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI. Results The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_Lactobacillus. Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing Lactobacillus) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process. Conclusions Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.

BackgroundThe public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood.MethodsThis study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale.FindingsThe outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels.InterpretationThe health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources.FundingThis work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Cardiac dysfunction frequently emerges in the initial stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model. Concurrently, these mice underwent a low-intensity exercise regimen to investigate its potential role in cardiac function during cachexia. Our findings indicate that exercise training can help prevent metastatic melanoma-induced muscle loss without significant alterations to body and fat weight. Moreover, exercise improved the melanoma-induced decline in left ventricular ejection fraction and fractional shortening, while also mitigating the increase in high-sensitive cardiac troponin T levels caused by metastatic melanoma in mice. Transcriptome analysis revealed that exercise significantly reversed the transcriptional alterations in the heart induced by melanoma, which were primarily enriched in pathways related to heart contraction. These results suggest that exercise can improve systolic heart function and directly influence the transcriptome of the heart during metastatic melanoma-induced cachexia.

Growing evidence indicates that severe tricuspid regurgitation (TR) is independently associated with adverse clinical outcomes. The prognostic benefit of isolated TR surgery remains unclear, and medical therapy for decompensated right heart failure alone cannot delay disease progression. TR assessment and management have substantially evolved in recent years. Currently, minimally invasive catheter-based techniques have emerged as a feasible and effective option for TR treatment in high-risk surgical patients. Transcatheter tricuspid valve edge-to-edge repair (T-TEER) has been proposed and applied as an interventional treatment for TR, and has yielded promising preliminary results. This review provides an overview of the current state of T-TEER.

Investigating the potential of macrophage efferocytosis has led to a growing interest in exploiting macrophage in immunotherapy. Macrophage-specific nano-medicines are currently being developed to stimulate the phagocytic clearance of apoptotic debris in atherosclerosis; however, these unnatural nanoparticles exhibit poor biocompatibility and limited efferocytosis activation ability. Here a pro-efferocytosis biomimetic nanorobot UM-EVLipo is developed based on nano-motor and extracellular vesicles (EVs) hybridized with plaque double-targeted liposomes. An elegant procedure with only 4 steps is integrated to prepare and purify these hybrid nanovesicles. It is first demonstrated that the EVs derived from bone marrow macrophages stimulated with IL-4 can promote the transformation of M0 and M1 macrophages into M2, an efferocytosis phenotype. Furthermore, the EVs hybridized with SHP-1 siRNA-liposomes blocked the "don't eat me" signal from apoptotic debris by intervening CD47-SIRP alpha-SHP-1 axis. This two-pronged strategy of resetting phenotype and blocking checkpoints furthest activates macrophage efferocytosis. Importantly, the urease motor increased the swimming speed of nanovesicles in the blood by 12.4 times, making it easier for them to penetrate the endothelial barrier. The UM-EVLipo accumulated within the atherosclerotic plaque, reactivate lesioned efferocytosis and reduce the plaque area in the carotid and coronary, which demonstrates the potential of a two-pronged strategy to prevent atherosclerotic cardiovascular disease.

Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (< 80 mg/dL), low-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L), lipoprotein(a) [Lp(a)] (< 30 mg/dL), triglycerides (< 1.7 mmol/L), remnant cholesterol (RC) (< 0.78 mmol/L), non-high-density lipoprotein cholesterol (< 2.6 mmol/L) at baseline and follow-up. Multivariate Cox regression models were employed to investigate the association between patient characteristics and target achievement. Among 4861 patients, the mean age was 64.9 years. Only 7.8 What is known? 1. Long-term prognosis of ACS remains challenging, underlining the need for optimisation of secondary prevention in these patients. 2. In addition to LDL-C, the residual lipid risk attributed to other atherogenic lipids is associated with increased risk after ACS. What the study adds? 1. Only 7.8 2. At follow-up, the proportions of the overall population and the very high-risk patients with LDL-C in the target range were 42.7 3. Patients with female sex, younger age, and comorbidities such as myocardial infarction, hypertension, and hypercholesterolemia were less likely to control their lipids.

Stroke is one of the most common causes of death and disability. In addition, most neuroprotective agents fail to rescue neurons from cerebral ischemic insults due to their poor ability to penetrate the blood-brain barrier (BBB). Here, the tailored engineered nanoenzyme has been successfully synthesized by coordination-driven co-assembly of dopamine (DA) and iron ion (Fe3+), which is subsequently camouflaged by neuron-specific rabies viral glycoprotein (RVG) peptide to scavenge reactive oxygen species (ROS) and inhibit inflammatory response in damaged neuron for the efficient therapy of ischemic stroke. The resulting nanoenzyme with good biocompatibility, core-shell structure, and suitable diameter can nondestructively cross the BBB and then internalize into the damaged neuron through the camouflaging and homologous targeted strategy of neuron-specific RVG peptide. After intravenous injection into transient middle cerebral artery occlusion (tMCAO) mouse models, nanoenzyme exerted a significant neuroprotective effect, resulting in a 50 % reduction in neurological scores and an approximate 33 % decrease in cerebral infarction volume. Interestingly, such nanoenzyme can eliminate free radicals, reduce neuroinflammation, enhance BBB integrity, improve mitochondrial function, and inhibit neuronal ferroptosis. Taken together, this well-designed nanoenzyme with its excellent biocompatibility and well-understood mechanisms holds promise a robust therapy for ischemic stroke.

Physical activities have beneficial effects on cardiovascular health, although the specific mechanisms are largely unknown. Cardiac resident macrophages (cMacs) and the distribution of their subsets are critical regulators for maintaining cardiovascular health and cardiac functions in both steady and inflammatory states. Therefore, we investigated the subsets of cMacs in mice after low-intensity exercise training to elucidate the exercise-induced dynamic changes of cMacs and the benefits of exercise for the heart. The mice were subjected to treadmill running exercise five days per week for five weeks using a low-intensity exercise training protocol. Low-intensity exercise training resulted in a suppression of body weight gain in mice and a significant increase in the ejection fraction, a parameter that represents the systolic function of the heart. Low-intensity exercise training induced the alterations in the transcriptome of the heart, which are associated with muscle contraction and mitochondrial function. Furthermore, low-intensity exercise training did not alter the number of lymphocyte antigen 6 complex, locus C1 (Ly6c)- cMacs but instead remodeled the distributions of Ly6c- cMac subsets. We observed an increase in the percentage of major histocompatibility complex class II (MHCII)low cMacs and a decrease in the percentage of MHCIIhigh cMacs in the heart after low-intensity exercise training. Therefore, the benefits of exercise for cardiovascular fitness might be associated with the redistribution of cMac subsets and the enhancement of the ejection fraction.