The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This 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. Findings: The 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. Interpretation: The 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. Funding: This 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).

Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice.

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.

CD163 protein inhibits lipopolysaccharide-induced macrophage transformation from M2 to M1 involved in disruption of the TWEAK-Fn14 interaction.

Macrophages play a crucial role in regulating inflammation and innate immune responses, and their polarization into distinct phenotypes, such as M1 and M2, is involved in various diseases. However, the specific role of CD163, a scavenger receptor expressed by macrophages, in the transformation of M2 to M1 macrophages remains unclear. Here, dexamethasone-induced M2 macrophages were treated with lipopolysaccharide (LPS) to induce the transformation of M2 to M1 macrophages. We found that treatment with lipopolysaccharide (LPS) induced the transformation of M2-like macrophages to an M1-like phenotype, as evidenced by increased mRNA levels of Il1b and Tnf, decreased mRNA levels of Cd206 and Il10, and increased TNF-α secretion. Knockdown of CD163 enhanced the phenotypic features of M1 macrophages, while treatment with recombinant CD163 protein (rmCD163) inhibited the LPS-induced M2-to-M1 transformation. Furthermore, LPS stimulation resulted in the activation of P38, ERK, JNK, and NF-κB P65 signaling pathways, and this activation was increased after CD163 knockdown and suppressed after rmCD163 treatment during macrophage transformation. Additionally, we observed that LPS treatment reduced the expression of CD163 in dexamethasone-induced M2 macrophages, leading to a decrease in the CD163-TWEAK complex and an increase in the interaction between TWEAK and Fn14. Overall, our findings suggest that rmCD163 can inhibit the LPS-induced transformation of M2 macrophages to M1 by disrupting the TWEAK-Fn14 interaction and modulating the MAPK-NF-κB pathway.

Low-intensity exercise training increases systolic function of heart and MHCII low cardiac resident macrophages.

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.

2023 Chinese expert consensus on the impact of COVID-19 on the management of cardiovascular diseases.

The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.

San-wei-tan-xiang capsule attenuates atherosclerosis by increasing lysosomal activity in adipose tissue macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Dyslipidemia is the leading risk factor of atherosclerosis (AS). Adipose tissue macrophages (ATMs) can regulate postprandial cholesterol levels via uptake and hydrolyzation of lipids and regulation of macrophage cholesterol efflux (MCE). San-wei-tan-xiang (SWTX) capsule, a Traditional Chinese medicine, exerts clinical benefits in patients with atherosclerotic cardiovascular diseases. AIM OF THE STUDY: This work is aimed to evaluate the chemical ingredients and mechanisms of SWTX in anti-AS. MATERIALS AND METHODS: The chemical ingredients of SWTX identified by liquid chromatography coupled with tandem mass spectrometry were used for network pharmacological analysis. The atheroprotective function of SWTX was evaluated in ApoE-/- mice fed a cholesterol-enriched diet. RESULTS: The chemical ingredients identified in SWTX were predicated to be important for lipid metabolism and AS. Animals studies suggested that SWTX effectively attenuated the atherosclerotic plaque growth, elevated postprandial HDL cholesterol levels, elevated the proportion of Tim4 and CD36-expressed ATMs, and upregulated the uptake of lipid and lysosomal activity in ATMs. SWTX-induced elevation of postprandial HDL cholesterol levels was dependent on increased lysosomal activity, since chloroquine, an inhibitor of lysosomal function, blocked the effect of SWTX. Lastly, some predicated bioactive compounds in SWTX can elevate lysosomal activity in vitro. CONCLUSION: SWTX could attenuate atherosclerotic plaque formation by elevating lysosomal activity and enhancing MCE in ATMs.

An "AND" Molecular Logic Gate as a Super-Enhancers for De Novo Designing Activatable Probe and Its Application in Atherosclerosis Imaging.

Developing activatable fluorescent probes with superlative fluorescence enhancement factor (F/F0 ) to improve the signal-to-noise (S/N) ratio is still an urgent issue. "AND" molecular logic gates are emerging as a useful tool for enhanced probes selectivity and accuracy. Here, an "AND" logic gate is developed as super-enhancers for designing activatable probes with huge F/F0 and S/N ratio. It utilizes lipid-droplets (LDs) as controllable background input and sets the target analyte as variable input. The fluorescence is tremendously quenching due to double locking, thus an extreme F/F0 ratio of target analyte is obtained. Importantly, this probe can transfer to LDs after a response occurs. The target analyte can be directly visualized through the spatial location without a control group. Accordingly, a peroxynitrite (ONOO- ) activatable probe (CNP2-B) is de novo designed. The F/F0 of CNP2-B achieves 2600 after reacting with ONOO- . Furthermore, CNP2-B can transfer from mitochondria to lipid droplets after being activated. The higher selectivity and S/N ratio of CNP2-B are obtained than commercial probe 3'-(p-hydroxyphenyl) fluorescein (HPFin vitro and in vivo. Therefore, the atherosclerotic plaques at mouse models are delineated clearly after administration with in situ CNP2-B probe gel. Such input controllable "AND" logic gate is envisioned to execute more imaging tasks.

Peroxynitrite/Lipid Droplet Sequence-Activated Dual-Lock Fluorescent Probes Enable Precise Intraoperative Imaging of Atherosclerotic Plaques.

The formation of atherosclerotic plaques is the root cause of various cardiovascular diseases (CVDs). Effective CVD interventions thus call for precise identification of the plaques to aid clinical assessment and treatment of such diseases. In this study, we introduced a dual-analyte sequentially activated logic fluorescence reporting system CNN2-B to precisely identify the atherosclerotic plaques in vivo. This probe was achieved by creating a dual-locked fluorescent sensor that permits highly specific and sensitive detection of peroxynitrite and lipid droplets─the two hallmarks of atherosclerosis (AS). The recognition group of the probe removed after reacting with ONOO- and intramolecular charge rearrangement occurred to generate a coumarin derivative structure. This structure had a strong solvent effect; it could recognize lipid droplets (LDs) in cells, thus exhibiting fluorescence without secondary molecular adjustment. The fluorescence was tremendously quenched by double locking; thus, an extreme fluorescence enhancement factor (F/F0) ratio of 365 for CNN2-B was obtained. Importantly, CNN2-B could move from the mitochondria to lipid droplets after being activated. CNN2-B exhibited higher selectivity and signal-to-noise (S/N) ratio than commercial probe hydroxyphenyl fluorescein (HPF). Therefore, atherosclerotic plaques in mouse models were delineated clearly by fluorescence imaging after in situ administration of CNN2-B.

Targeting WWP1 ameliorates cardiac ischemic injury by suppressing KLF15-ubiquitination mediated myocardial inflammation.

Rationale: Previous studies have suggested that myocardial inflammation plays a critical role after ischemic myocardial infarction (MI); however, the underlying mechanisms still need to be fully elucidated. WW domain-containing ubiquitin E3 ligase 1 (WWP1) is considered as an important therapeutic target for cardiovascular diseases due to its crucial function in non-ischemic cardiomyopathy, though it remains unknown whether targeting WWP1 can alleviate myocardial inflammation and ischemic injury post-MI. Methods: Recombinant adeno-associated virus 9 (rAAV9)-cTnT-mediated WWP1 or Kruppel-like factor 15 (KLF15) gene transfer and a natural WWP1 inhibitor Indole-3-carbinol (I3C) were used to determine the WWP1 function in cardiomyocytes. Cardiac function, tissue injury, myocardial inflammation, and signaling changes in the left ventricular tissues were analyzed after MI. The mechanisms underlying WWP1 regulation of cardiomyocyte phenotypes in vitro were determined using the adenovirus system. Results: We found that WWP1 expression was up-regulated in cardiomyocytes located in the infarct border at the early phase of MI and in hypoxia-treated neonatal rat cardiac myocytes (NRCMs). Cardiomyocyte-specific WWP1 overexpression augmented cardiomyocyte apoptosis, increased infarct size and deteriorated cardiac function. In contrast, inhibition of WWP1 in cardiomyocytes mitigated MI-induced cardiac ischemic injury. Mechanistically, WWP1 triggered excessive cardiomyocyte inflammation after MI by targeting KLF15 to catalyze K48-linked polyubiquitination and degradation. Ultimately, WWP1-mediated degradation of KLF15 contributed to the up-regulation of p65 acetylation, and activated the inflammatory signaling of MAPK in ischemic myocardium and hypoxia-treated cardiomyocytes. Thus, targeting of WWP1 by I3C protected against cardiac dysfunction and remodeling after MI. Conclusions: Our study provides new insights into the previously unrecognized role of WWP1 in cardiomyocyte inflammation and progression of ischemic injury induced by MI. Our findings afford new therapeutic options for patients with ischemic cardiomyopathy.

The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies.

The solute carrier family 12 (SLC12) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl- extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl- loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer 36Cl-, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, 22Na+ uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments.

An overview of PAX1: Expression, function and regulation in development and diseases.

Transcription factors play multifaceted roles in embryonic development and diseases. PAX1, a paired-box transcription factor, has been elucidated to play key roles in multiple tissues during embryonic development by extensive studies. Recently, an emerging role of PAX1 in cancers was clarified. Herein, we summarize the expression and functions of PAX1 in skeletal system and thymus development, as well as cancer biology and outline its cellular and molecular modes of action and the association of PAX1 mutation or dysregulation with human diseases, thus providing insights for the molecular basis of congenital diseases and cancers.

Clinical Manifestation of Cardiac Rupture in Patients with ST-Segment Elevation Myocardial Infarction: Early Versus Late Primary Percutaneous Coronary Intervention.

Background: Cardiac rupture is one of the fatal complications of ST-Segment Elevation Myocardial Infarction (STEMI) in the primary percutaneous coronary intervention (PPCI) era. The present study aims to identify risk factors of cardiac rupture among patients suffering from STEMI, treated with early and late PPCI. Methods: This is a multicenter retrospective cohort study involving STEMI patients with cardiac rupture (CR group), matched with STEMI patients without CR (control group) in a 1:5 ratio. They were divided into the early (≤ 6 h) and the late (> 6 h) PCI groups. Multivariable logistic regression was utilized to identify risk factors for cardiac rupture. Results: Seventy-four patients in the CR and 370 in the control group were included. Multivariable regression identified lateral infarction (OR = 11.89, 95% CI 2.22-63.81, p < 0.01) in the early PCI phase as a significant risk factor for cardiac rupture. Thrombolysis in myocardial infarction (TIMI) grade 0-1 (early PCI: OR = 4.16, 95% CI 1.33-13.0, p = 0.01; late PCI: OR = 4.46, 95% CI 1.59-12.54, p < 0.01) was a risk factor for both early and late PCI groups. In contrast, TIMI grade 2 was associated with a higher rupture risk within the late (OR = 16.87, 95% CI 3.83-74.19, p < 0.001) but not for the early (OR = 5.44, 95% CI 0.76-39.07, p = 0.09) PCI groups. STEMI combined with Killip IV was associated with a higher rupture risk for the late PCI group (OR = 1.43, 95% CI 1.03-1.99, p = 0.04). Intra-aortic balloon pump (IABP) was protective against cardiac rupture within early PPCI (OR = 0.18, 95% CI 0.04-0.89, p = 0.04). In contrast, glycoprotein IIb/IIIa inhibitors were associated with lower rupture risks in both the early and late groups (early PCI: OR = 0.38, 95% CI 0.17-0.87, p = 0.02; late PCI: OR = 0.33, 95% CI 0.15-0.75, p < 0.01). Conclusions: No reflow or slow blood flow is associated with a higher risk of cardiac rupture in early and late PCI patients. Glycoprotein IIb/IIIa inhibitors are beneficial in preventing heart rupture, and the use of IABP in early PPCI is also helpful in preventing heart rupture.

Association Between Serum Uric Acid Levels and Traditional Cardiovascular Risk Factors in Xiamen Residents of China: A Real-World Study.

Background: Serum uric acid (SUA) levels was associated with cardiovascular diseases and cardiovascular events. However, the relationship between SUA levels and traditional cardiovascular risk factors has not been well-established among Xiamen residents. Our study aimed to estimate the relationship between SUA levels and cardiovascular risk factors among Xiamen residents using real-world data. Methods: Participants were enrolled from eight community health service centers in Xiamen, China. Participants were divided into four groups according to quartiles of the SUA levels. The history of diseases, the use of medications and the levels of laboratory parameters were collected. The China-PAR equation was used to evaluate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Results: A total of 1,322 participants were enrolled. About 568 (43.0%) were men and 754 (57.0%) were women. The prevalences of hypertension, elderly, current smokers, and obesity were higher in the quartile 4 (Q4) group than the quartile 1 (Q1) group (all p < 0.001). Multivariable logistic regression analysis showed the OR for hypertension was 2.671 (95% CI 1.777-4.015, p < 0.001) in the Q4 group compared with that in the Q1 group. Further logistic regression showed the OR for hypertension was 3.254 (95% CI 1.756-6.031, p < 0.001) in men and 2.314 (95% CI 1.354-3.955, p = 0.002) in women in the Q4 group compared with that in the Q1 group, respectively. In addition, the percentage of participants with low 10-year ASCVD risk calculated by China-PAR was higher in the Q1 group than that in the Q4 group (55.86 vs. 31.82%, p < 0.001). The percentage of participants with high 10-year ASCVD risk was lower in the Q1 group compared with the Q4 group (15.32 vs. 25.45%, p < 0.001). Multiple linear logistic regression showed the 10-year China-PAR ASCVD risk scores was positively correlated with SUA after adjusting for various factors (ß = 0.135, p = 0.001). Conclusion: Serum uric acid was associated with several cardiovascular risk factors in Xiamen residents. The percentage of high 10-year ASDVD risk was higher in participants with hyperuricemia. Participants with hyperuricemia may experience cardiovascular benefit from uric acid-lowering therapy.

Efficacy and Dosage Pattern of Sacubitril/Valsartan in Chinese Heart Failure with Reduced Ejection Fraction Patients.

This study aims to investigate the dosage pattern, efficacy, and safety of sacubitril/valsartan (Sac/Val) in Chinese heart failure with reduced ejection fraction (HFrEF) patients regarding real-world settings. Patients from 27 centers with a confirmed diagnosis of HFrEF and initiated Sac/Val treatment were enrolled. The primary objective was to evaluate the dosage pattern and change of heart failure status. In a final cohort of 983 patients, outpatient Sac/Val treatment demonstrated a similar beneficial effect in NT-proBNP and cardiac function. After initiating the treatment, overall and sub-population showed similar safety and efficacy. Patients who received a higher dose of Sac/Val (> 200 mg/d) demonstrated better improvement in LV function and reduction of NT-proBNP regardless of adjustment. Among Chinese HFrEF patients, Sac/Val showed a comparable reduction in NT-proBNP and improvement in cardiac function. Data further support guideline recommendations of Sac/Val in Chinese population. Optimal up-titration might provide further benefits. Further long-term and prognostic studies are needed.

The Efficacy and Safety of Phase I Cardiac Rehabilitation in Patients Hospitalized in Cardiac Intensive Care Unit With Acute Decompensated Heart Failure: A Study Protocol for a Randomized, Controlled, Clinical Trial.

Background: Cardiac rehabilitation (CR) improves outcomes in patients with heart failure. However, data on CR efficacy in patients with acute decompensated heart failure is limited. This study is designed to assess the efficacy and safety of CR in patients hospitalized in cardiac intensive care unit (CICU) with acute decompensated heart failure (ADHF). Methods: This is a single-center, randomized controlled, single-blind clinical trial. A total of 120 participants hospitalized in CICU with ADHF will be randomly allocated in the ratio of 1:1 to two groups: CR group and control group. Participants will receive tailored and progressive CR intervention or attention control. The CR intervention include personalized breathing training, small muscle group resistance training, and aerobic endurance training based on the physical fitness assessment results. The subjects will receive the CR training for 5 days and will be followed up for 6 months. The primary endpoints are the score of the short physical performance battery (SPPB) and 6-month all-cause rehospitalization. The secondary endpoints include cardio-pulmonary function, activities of daily living (ADL), in-hospital mortality rate and 6-month all-cause mortality rate. Discussion: This randomized, controlled, clinical trial will assess whether CR improves physical function and reduces rehospitalization in patients hospitalized in CICU with ADHF. The results will provide further research-based evidence for the clinical application of CR in patients with ADHF. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100050151. Registered on 19 August 2021.

Enzyme Catalysis Biomotor Engineering of Neutrophils for Nanodrug Delivery and Cell-Based Thrombolytic Therapy.

Utilizing neutrophils (NEs) to target and deliver nanodrugs to inflammation sites has received considerable attention. NEs are involved in the formation and development of thrombosis by transforming into neutrophil extracellular traps (NETs); this indicates that NEs may be a natural thrombolytic drug delivery carrier. However, NEs lack an effective power system to overcome blood flow resistance and enhance targeting efficiency. Herein, we report the application of a urease catalysis micromotor powered NEs nanodrug delivery system to promote thrombolysis and suppress rethrombosis. The urease micromotor powered Janus NEs (UM-NEs) were prepared by immobilizing the enzyme asymmetrically onto the surface of natural NEs and then loading urokinase (UK) coupled silver (Ag) nanoparticles (Ag-UK) to obtain the UM-NEs (Ag-UK) system. Urease catalytic endogenous urea is used to generate thrust by producing ammonia and carbon dioxide, which propels NEs actively targeting the thrombus. The UM-NEs (Ag-UK) can be activated by enriched inflammatory cytokines to release NETs at the thrombosis site, resulting in a concomitant release of Ag-UK. Ag-UK induces thrombolysis to restore vascular recanalization. This urease micromotor-driven NEs drug delivery system can significantly reduce the hemorrhagic side effects, promote thrombolysis, and inhibit rethrombosis with high bioavailability and biosafety, which can be used for the treatment of thrombotic diseases.

Emerging roles of sortilin in affecting the metabolism of glucose and lipid profiles.

Dyslipidemia has recently been identified as an important factor in modulating the progression of several health conditions, grouped as cardio-metabolic syndrome and including obesity,insulin resistance, and atherosclerosis. Among multiple factors which regulate the development of cardio-metabolic syndrome, sortilin has been found in multiple cell types, such as adipocyte, hepatocyte, and macrophage, suggesting that sortilin is correlated to the development and the severity of cardio-metabolic syndrome. Consistently, several genome-wide association  (GWAS) and basic experimental research studies are being conducted to find novel gene loci involved in regulating the pathological progression of cardio-metabolic syndrome. According to these data, both SORT1 gene and sortilin protein have an important function in regulating the circulating lipid and glucose metabolism resulting in modulation of disease progression. In this comprehensive review, we summarize the recent research results in regards to sortilin function in modulating the circulating lipid and glucose metabolism. Moreover, we also discuss and analyze the emerging evidence elucidating the potential mechanisms by which sortilin affects synthesis and secretion of lipid and glucose.

The proGnostic role of caRdiac rehAbilitation in patients with left ventriCular anEurysm formation after anterior myocardial infarction (the GRACE study): Study rationale and design of a prospective randomized controlled trial.

Background: Cardiac rehabilitation (CR) is an essential intervention after acute myocardial infarction (MI). However, it is still unclear whether patients with left ventricular aneurysm (LVA) formation after anterior MI would benefit from CR programs. This clinical trial is designed to assess the role of CR in patients with LVA formation after anterior MI. Trial design: The GRACE study is a single-center, single-blind, prospective, randomized controlled clinical trial in China. 100 subjects aged 18-75 years with LVA formation after anterior MI will be recruited and randomized 1:1 to the CR or control group. Both groups will receive standard drug treatment and routine health education according to the guidelines. Participants in the CR group will additionally receive tailored CR programs delivered over a period of 36 sessions. These participants will then be followed up for 1-year. The primary outcome is peak oxygen uptake measured by cardiopulmonary exercise testing after CR programs. The secondary outcomes are cardiac function and EuroQol 5-Dimension-3 Level index scores after CR program and 1-year and major adverse cardiac cerebrovascular events, a composite of cardiovascular mortality, non-fatal MI, non-fatal stroke, malignant arrhythmia or hospitalization for heart failure during the follow-up period. Conclusions: This single-center, single-blind, prospective, randomized controlled clinical trial will determine whether CR improves physical capacity and clinical outcomes in patients with LVA formation after anterior MI. Trial registration: Chinese Clinical Trial Registry ChiCTR2200058852. Registered on 18 April 2022.

PiRNA pathway in the cardiovascular system: a novel regulator of cardiac differentiation, repair and regeneration.

Piwi-interacting RNAs (piRNAs) are a novel group of small non-coding RNA molecules with lengths of 21-35 nucleotides, first identified from the germline. PiRNAs and their associated PIWI clade Argonaute proteins constitute a key part of the piRNA pathway, with the best-known biological function to silence transposable elements in germ cells. The piRNA pathway, in fact, is not exclusive to the germline. Somatic functions of piRNAs have been recorded since their first discovery. To date, involvement of the piRNA pathway has been identified within the biological functions of genome rearrangement, epigenetic regulation, protein regulation in the germline and/or the soma transcriptionally or post-transcriptionally. Emerging evidence has shown that the piRNA pathway is essential for the normal function of the cardiovascular system and that its abnormal expression is correlated with cardiovascular dysfunction, although comprehensive roles of the piRNA pathway in the cardiovascular system and underlying mechanisms remain unclear. In this review, we discuss current findings of piRNA pathway expression in cardiac cell types and their potential functions in cardiac differentiation, repair and regeneration, thus providing new insights into cardiovascular disease development associated with the piRNA pathway.