The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers.

BACKGROUND AND AIMS: Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD). METHODS: The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics. RESULTS: Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (ß = 0.86, P < 0.001) and WBC (ß = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients. CONCLUSION: Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.

A bibliometric analysis of PCSK9 inhibitors from 2007 to 2022.

Background: Since the approval of the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for marketing in 2015, PCSK9 inhibitors have attracted significant interest in the field of cardiovascular endocrinology. A large number of clinical trials have confirmed the efficacy and safety of PCSK9 inhibitors in reducing cholesterol and the risk of cardiovascular events. No bibliometric analysis of PCSK9 inhibitors has been performed as of yet. This study aims to analyze the research trends and hotspots of PCSK9 inhibitors through bibliometric analysis. Methods: We searched the Web of Science Core Collection (WoSCC) database for PCSK9 inhibitor-related publications from 2007 to 2022. Data visualization analysis was performed using CiteSpace software. Microsoft Excel and Graphpad software were used for the drawing of some tables and figures. Results: A total of 1072 pieces of literature were retrieved between 2007 and 2022. The number of publications concerning PCSK9 inhibitors is growing annually. The top five countries with the most articles published were the United States, England, Canada, Italy, and France. Harvard University, Amgen, Brigham & Women's Hospital, Harvard Medical School, and Imperial College London are the five institutions with the highest output. The Journal of Clinical Lipidology is the most popular journal in this field. The most frequently cited journal is the New England Journal of Medicine. As for authors, Sabatine MS and Giugliano RP from Brigham & Women's Hospital have the highest number of published articles. Amgen is the funding agency for most of the research. According to keyword analysis, "low density lipoprotein", "familial hypercholesterolemia", "PCSK9 inhibitor", "PCSK9", and "efficacy" are the five keywords with the highest frequency of co-occurrence. Conclusion: The past 15 years have witnessed a rapid and fruitful development of PCSK9 inhibitors. The research trend and focus for PCSK9 inhibitors are from the mechanism of reducing low-density lipoprotein cholesterol to related clinical trials. Developed countries such as the United States have contributed prominently in this area. Coronary artery and inflammation are currently at the forefront of research in the field and are in an explosion period.

The association of statin therapy and cancer: a meta-analysis.

BACKGROUND: Statins are routinely prescribed to lower cholesterol and have been demonstrated to have significant benefits in atherosclerotic cardiovascular disease. However, whether statin therapy has effects on cancer risk remains controversial. In this study, we investigated the influence of statin therapy on cancer incidence and mortality by conducting a comprehensive meta-analysis of randomized controlled trials. METHODS: Systematic searches by Cochrane, Embase, Medline, and PubMed were performed to locate data from eligible randomized controlled trials related to statin therapy and oncology. Our main endpoints were cancer incidence and mortality. Fixed-effects models were used in this study. RESULTS: This meta-analysis comprised thirty-five randomized controlled studies. Twenty-eight included studies reported cancer incidence, and eighteen reported cancer mortality. The pooled results indicated no reduction in cancer incidence with statins compared to placebo [OR = 0.99, 95% CI (0.95, 1.03)]. In addition, statins did not decrease cancer mortality [OR = 0.99, 95% CI (0.91, 1.07)]. This study also performed a number of subgroup analyses, which showed no effect of statins on cancer subtypes such as genitourinary and breast cancer. Neither the type of statin nor long-term treatment with statins had an effect on cancer incidence and mortality. CONCLUSION: Through comprehensive analysis, we found that statin therapy does not reduce cancer incidence or mortality while protecting the cardiovascular system. TRIAL REGISTRATION: Prospero CRD42022377871.

Correlation between serum soluble ASGR1 concentration and low-density lipoprotein cholesterol levels: a cross-sectional study.

BACKGROUND: Recent studies have shown that loss-of-function mutations in hepatic asialoglycoprotein receptor 1 (ASGR1) are associated with low levels of circulating cholesterol and a reduced risk of coronary artery disease (CAD). In contrast to ASGR1 on the hepatocyte membrane, serum soluble ASGR1 (sASGR1) is a secreted form that has been detected in circulation. However, the functions of serum sASGR1 are unclear. This study aims to investigate the relationship between human serum sASGR1 concentration and low-density lipoprotein cholesterol (LDL-C) levels. METHODS: In a cohort of 134 participants who underwent coronary angiography examination, basic information was recorded, and blood samples were collected for biochemical testing. The serum sASGR1 concentration was determined by ELISA kits. The relationship between sASGR1 concentration and LDL-C levels was examined using linear regression models and interaction tests. Univariate and multivariate analyses were used to identify clinical variables that affect sASGR1 levels. RESULTS: After adjusting for potential confounders such as age, sex, BMI, and statin use, the serum sASGR1 concentration was positively correlated with LDL-C levels (ß = 0.093, 95% CI: 0.04 to 0.14, P < 0.001). Subgroup analysis and interaction tests showed that the effect of serum sASGR1 concentration on LDL-C levels was significantly influenced by hypertension status (P for interaction = 0.0067). The results of a multivariate linear regression analysis incorporating age, serum TG, LDL-C, nonesterified fatty acid (NEFA), white blood cell counts (WBCC), and fibrinogen revealed that LDL-C (ß = 1.005, 95% CI: 0.35 to 1.66, P = 0.003) and WBCC (ß = 0.787, 95% CI: 0.41 to 1.16, P < 0.0001) were independent influencing factors for serum sASGR1 levels. CONCLUSIONS: The serum sASGR1 concentration was positively correlated with LDL-C levels. In addition, hypertension status significantly affected the effect of serum sASGR1 on LDL-C levels. This study provides some research ideas for clinical doctors and researchers, as well as some references for additional research on serum sASGR1.

Current understanding of the contribution of lactate to the cardiovascular system and its therapeutic relevance.

Research during the past decades has yielded numerous insights into the presence and function of lactate in the body. Lactate is primarily produced via glycolysis and plays special roles in the regulation of tissues and organs, particularly in the cardiovascular system. In addition to being a net consumer of lactate, the heart is also the organ in the body with the greatest lactate consumption. Furthermore, lactate maintains cardiovascular homeostasis through energy supply and signal regulation under physiological conditions. Lactate also affects the occurrence, development, and prognosis of various cardiovascular diseases. We will highlight how lactate regulates the cardiovascular system under physiological and pathological conditions based on evidence from recent studies. We aim to provide a better understanding of the relationship between lactate and cardiovascular health and provide new ideas for preventing and treating cardiovascular diseases. Additionally, we will summarize current developments in treatments targeting lactate metabolism, transport, and signaling, including their role in cardiovascular diseases.

Differences in right ventricular function and response to targeted therapy between patients with IPAH and PAH-CHD.

Background and aims: Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disorder characterized by elevated pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP). Right heart failure is a life-threatening complication of PAH and predicts a poor prognosis. PAH associated with congenital heart disease (PAH-CHD) and idiopathic PAH (IPAH) are two prevalent PAH subtypes in China. In this section, we set out to explore baseline right ventricular (RV) function and its response to targeted agents between IPAH and PAH-CHD. Methods and results: Consecutive patients diagnosed with IPAH or PAH-CHD by right heart catheterization (RHC) in the Second Xiangya Hospital from November 2011 to June 2020 were included. All patients received PAH-targeted therapy and the RV function was assessed by echocardiography at baseline and during follow-up. A total of 303 patients (age, 36.23 ± 13.10 years; women, 213 (70.3%); mean PAP [mPAP], 63.54 ± 16.12 mmHg; PVR, 14.74 ± 7.61 WU) with IPAH (n = 121) or PAH-CHD (n = 182) were included in this study. Compared with PAH-CHD, patients with IPAH had worse baseline RV function. As of the latest follow-up, forty-nine patients with IPAH and six patients with PAH-CHD died. Kaplan-Meier analyses showed better survival in PAH-CHD versus IPAH. After PAH-targeted therapy, patients with IPAH had less improvement in 6 MWD, World Health Organization functional class, and RV functional parameters compared with patients with PAH-CHD. Conclusion: Compared with patients with PAH-CHD, patients with IPAH had worse baseline RV function, unfavourable prognosis, and inadequate response to targeted treatment.

Role of ACSL5 in fatty acid metabolism.

Free fatty acids (FFAs) are essential energy sources for most body tissues. A fatty acid must be converted to fatty acyl-CoA to oxidize or be incorporated into new lipids. Acyl-CoA synthetase long-chain family member 5 (ACSL5) is localized in the endoplasmic reticulum and mitochondrial outer membrane, where it catalyzes the formation of fatty acyl-CoAs from long-chain fatty acids (C16-C20). Fatty acyl-CoAs are then used in lipid synthesis or ß-oxidation mediated pathways. ACSL5 plays a pleiotropic role in lipid metabolism depending on substrate preferences, subcellular localization and tissue specificity. Here, we review the role of ACSL5 in fatty acid metabolism in multiple metabolic tissues, including the liver, small intestine, adipose tissue, and skeletal muscle. Given the increasing number of studies suggesting the role of ACSL5 in glucose and lipid metabolism, we also summarized the effects of ACSL5 on circulating lipids and insulin resistance.

Efficacy and safety of sequential combination therapy for pulmonary arterial hypertension: A meta-analysis of Randomized-Controlled Trials.

BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH) combination therapy pooled sequential and initial combination together, which might threaten their authenticity and clinical significance for the difference between two strategies. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sequential combination therapy (SCT) with background therapy (BT) in PAH patients. Raw data were extracted to calculate risk ratio (RR) or weighted mean difference (WMD) for predefined efficacy and safety outcomes. Mantel-Haenszel fixed or random effects model was used based on heterogeneity. RESULTS: 17 RCTs involving 4343 patients (97.2% of patients with WHO-FC II-III) were included. SCT decreased clinical worsening (RR 0.66, 95% CI 0.58 to 0.76), nonfatal clinical worsening (RR 0.61, 95% CI 0.52 to 0.71), functional class (decrease of 28% in the portion of patients with WHO-FC worsening and increase of 33% in the portion of patients with WHO-FC improvement), and increased 6-min walk distance (WMD 17.68 m, 95% CI 10.16 to 25.20), but didn't reduce mortality, lung transplantation, admission to hospital, and treatment escalation compared with BT. Although any adverse event and serious adverse event were similar between SCT and BT, SCT increased all-cause treatment discontinuation (RR 1.49, 95% CI 1.30 to 1.71) and drug-related treatment discontinuation (RR 2.30, 95% CI 1.86 to 2.84) with higher incidence of headache, flushing, nausea, diarrhoea and jaw pain. CONCLUSIONS: For WHO-FC II-III PAH patients who have established BT, our study reinforced the recommendation of SCT to improve clinical worsening, functional status, and exercise capacity, although with higher incidence of side-effects and withdrawal.

Role of Gut Microbiota in Pulmonary Arterial Hypertension.

Gut microbiota and its metabolites play an important role in maintaining host homeostasis. Pulmonary arterial hypertension (PAH) is a malignant clinical syndrome with a frightening mortality. Pulmonary vascular remodeling is an important feature of PAH, and its pathogenesis is not well established. With the progress of studies on intestinal microbes in different disease, cumulative evidence indicates that gut microbiota plays a major role in PAH pathophysiology. In this review, we will systematically summarize translational and preclinical data on the correlation between gut dysbiosis and PAH and investigate the role of gut dysbiosis in the causation of PAH. Then, we point out the potential significance of gut dysbiosis in the diagnosis and treatment of PAH as well as several problems that remain to be resolved in the field of gut dysbiosis and PAH. All of this knowledge of gut microbiome might pave the way for the extension of novel pathophysiological mechanisms, diagnosis, and targeted therapies for PAH.

Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China.

The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease-associated PAH (CHD-PAH) and 20 healthy controls were collected and analysed by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Orthogonal partial least square-discriminate analysis (OPLS-DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)-induced PAH rat model. The OPLS-DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD-PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS-DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N-acetylcholine-d-sphingomyelin, oleic acid, palmitic acid and 2-Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real-time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT-1 in right heart/lung were significantly up-regulated in MCT group than the control group.

Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management.

With an increasing global burden of coronary artery disease (CAD), early detection and timely management of risk factors are crucial to reduce morbidity and mortality in such patients. Diabetes mellitus (DM) is considered an independent risk factor for the development of CAD. Metformin, an anti-diabetic drug, has been shown in pre-clinical and clinical studies, to lower the cardiovascular events in the DM patients. Growing evidence suggests that metformin has a protective effect on coronary artery beyond its hypoglycemic effects. Given its global availability, route of administration and cost, metformin provides an alternate/additional therapeutic option for primary and secondary prevention of CAD in DM and non-diabetics alike. Future prospective cohort-based studies and randomized clinical trials are needed to identify 'at-risk' population who may potentially benefit from metformin.

Multivessel Coronary Revascularization Strategies in Patients with Chronic Kidney Disease: A Meta-Analysis.

BACKGROUND: Early revascularization can lead to better prognosis in multivessel coronary artery disease (CAD) patients with chronic kidney disease (CKD). However, whether coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is better remains unknown. METHODS: We searched PubMed and the Cochrane Library database from inception until December 9, 2017, for articles that compare outcomes of CABG and PCI in multivessel CAD patients with CKD. We pooled the odds ratios with a fixed-effects model when I2 < 50% or a random-effects model when I2 > 75% and conducted heterogeneity and quality assessments as well as publication bias analyses. RESULTS: A total of 17 studies with 62,343 patients were included. Compared with CABG, the pooled analysis showed that PCI had a lower risk of short-term all-cause death (OR, 0.56; 95% CI, 0.37-0.84) and cerebrovascular accidents (OR, 0.65; 95% CI, 0.53-0.79) but a higher risk of cardiac death (OR, 1.29; 95% CI, 1.21-1.37), myocardial infarction (MI) (OR, 1.73; 95% CI, 1.35-2.21), and repeat revascularization (RR) (OR, 3.9; 95% CI, 2.99-5.09). There was no significant difference in the risk of long-term all-cause death (OR, 1.08; 95% CI, 0.95-1.23) and major adverse cardiac and cerebrovascular events (MACCE) (OR, 1.58; 95% CI, 0.99-2.52) between the PCI and CABG groups. A subgroup analysis restricted to patients treated with dialysis or with PCI-drug-eluting stent yielded similar results. CONCLUSIONS: PCI for patients with CKD and multivessel disease (multivessel CAD) had advantages over CABG with regard to short-term all-cause death and cerebrovascular accidents, but disadvantages regarding the risk of myocardial death, MI, and RR; there was no significant difference in the risk of long-term all-cause death and MACCE. Large randomized controlled trials are needed to confirm our findings.

ANGPTL3 possibly promotes cardiac angiogenesis through improving proangiogenic ability of endothelial progenitor cells after myocardial infarction.

Angiopoietin Like protein 3 (ANGPTL3) is at present considered as a central molecular target for therapy designed to reduce atherogenic lipids and atherosclerosis. However, concerns about the safety of inactivation of ANGPTL3 in patients with coronary artery disease (CAD) especially myocardial infarction (MI) have been raised. ANGPTL3 is reported to possess proangiogenic property. Angiogenesis is critical to the recovery of MI. Endothelial progenitor cells (EPCs) have multiple differentiation potential and play an important role in the angiogenesis post-MI. Promoting the function of EPCs could facilitate the angiogenesis and recovery of MI. Previous studies have shown that ANGPTL3 can promote angiogenesis in corneal of rats and promote angiogenesis of endothelial cells by binding to integrin ανß3 receptors and promoting phosphorylation of protein kinase B (AKT). Our institution found that activated AKT can up-regulate the expression of microRNA-126 (miR-126), which can promote the proangiogenic ability of EPCs. The integrin ανß3 receptors and AKT also express in EPCs and are closely related to proangiogenic function. Therefore, we hypothesized that ANGPTL3 could improve function of EPCs by binding to integrin ανß3 receptors and up-regulating miR-126 expression via activating AKT, thus promoting the formation of new blood vessels, attenuating myocardial ischemia and improving heart function.