The Correlation Between Whole Blood Copper (Cu), Zinc (Zn) Levels and Cu/Zn Ratio and Sepsis-Induced Left Ventricular Systolic Dysfunction (SILVSD) in Patients with Septic Shock: A Single-Center Prospective Observational Study.

Purpose: This study aimed to explore relationships between whole blood copper (Cu), zinc (Zn) and Cu/Zn ratio and cardiac dysfunction in patients with septic shock.

Subjects And Methods: Between April 2018 and March 2020, septic shock patients with sepsis-induced left ventricular systolic dysfunction (SILVSD, left ventricular ejection fraction, LVEF<50%) and with no sepsis-induced myocardial dysfunction (non-SIMD, septic shock alone and LVEF>50%) and controls were prospectively enrolled. Whole blood Cu and Zn levels were measured using flame atomic absorption spectrophotometry.

Cardiac-specific deletion of FDPS induces cardiac remodeling and dysfunction by enhancing the activity of small GTP-binding proteins.

The mevalonate pathway is essential for cholesterol biosynthesis. Previous studies have suggested that the key enzyme in this pathway, farnesyl diphosphate synthase (FDPS), regulates the cardiovascular system. We used human samples and mice that were deficient in cardiac FDPS (c-Fdps mice) to investigate the role of FDPS in cardiac homeostasis.

Identification and Functional Prediction of Long Non-Coding RNAs in Dilated Cardiomyopathy by Bioinformatics Analysis.

Dilated cardiomyopathy (DCM) is a relatively common cause of heart failure and the leading cause of heart transplantation. Aberrant changes in long non-coding RNAs (lncRNAs) are involved in DCM disorder; however, the detailed mechanisms underlying DCM initiation and progression require further investigation, and new molecular targets are needed. Here, we obtained lncRNA-expression profiles associated with DCM and non-failing hearts through microarray probe-sequence re-annotation.

A Variant in the Nicotinic Acetylcholine Receptor Alpha 3 Subunit Gene Is Associated With Hypertension Risks in Hypogonadic Patients.

gene knockout causes hypertension in castrated mice. EPHB6 controls catecholamine secretion by adrenal gland chromaffin cells (AGCCs) in a testosterone-dependent way. Nicotinic acetylcholine receptor (nAChR) is a ligand-gated Ca/Na channel, and its opening is the first signaling event leading to catecholamine secretion by AGCCs.

MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)‑induced VSMC phenotype switch, and to investigate the underlying mechanism.

Comparison of transesophageal echocardiography findings after different anticoagulation strategies in patients with atrial fibrillation: a systematic review and meta-analysis.

Background: High risk of embolic events exists in both patients with chronic atrial fibrillation (AF) and patients in the perioperative period of ablation (effective treatment for AF). Therefore, anticoagulant therapy is important. Oral anticoagulants can be divided into two major categories: vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs).

Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.

Several members of the EPH kinase family and their ligands are involved in blood pressure regulation, and such regulation is often sex- or sex hormone-dependent, based on animal and human genetic studies. EPHB6 gene knockout (KO) in mice leads to hypertension in castrated males but not in un-manipulated KO males or females. To assess whether this finding in mice is relevant to human hypertension, we conducted a human genetic study for the association of EPHB6 and its two ligands, EFNB1 and EFNB3, with hypertension in hypogonadic patients.

The Role of RhoA in Neovascular-Related Functions of Endothelial Progenitor Cells Induced by AngiotensinⅡ.

Background/aims: Interference with endothelial progenitor cell (EPC) neovascularization is a novel therapeutic target for neovascular-related diseases. Angiotensin Ⅱ (Ang Ⅱ) was found to enhance new vessel formation and aggravated neovascular-related diseases. In this study, we investigated the effects of Ang Ⅱ on EPC neovascular-related functions and explored the underlying mechanisms.

Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.

Background: Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs.

Methods: We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo.

Abnormal expression of long non-coding RNAs in myocardial infarction.

Myocardial infarction (MI) is the leading cause of fatality worldwide. Our study aimed to investigate the dysregulated long non-coding RNA (lncRNA) in MI and elucidate the mechanism of it in MI. The lncRNA and mRNA expression profiling of the whole left ventricular tissue of MI mice model (8 mice) and Sham group (8 mice) was obtained based on microarray analysis.

Congenital giant left atrial appendage aneurysm: a case report.

Background: Congenital left atrial appendage aneurysm (LAAA) is a rare cardiac anomaly with potentially serious complications, including life-threatening systemic thromboembolism, atrial tachyarrhythmia, and cardiac dysfunction. Currently, early surgical intervention is generally recommended to prevent these complications.

Case Presentation: We present a case of congenital giant LAAA in a female patient who successfully completed pregnancy and underwent caesarean section with no obvious complications.

Inhibition of farnesyl pyrophosphate synthase improves pressure overload induced chronic cardiac remodeling.

Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. In our previous studies, we find that inhibition of FPPS attenuates angiotensin II-induced cardiac hypertrophy and fibrosis by suppressing RhoA while FPPS and Ras are up-regulated in pressure overload rats. In this study, we evaluate the effects and mechanisms of FPPS inhibition in pressure overload mice.

Farnesyl pyrophosphate synthase inhibitor, ibandronate, improves endothelial function in spontaneously hypertensive rats.

Reactive oxygen species (ROS), originating predominantly from vascular smooth muscle cells (VSMCs), lead to vascular damage and endothelial dysfunction in rats with hypertension. The downstream signaling pathways of farnesyl pyrophosphate (FPP) synthase, Ras-related C3 botulinum toxin substrate 1 (Rac1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mediate the generation of ROS. The present study investigated the effect of the FPP synthase inhibitor, ibandronate, on ROS production, the possible beneficial effect on endothelial dysfunction and the underlying mechanisms in spontaneously hypertensive rats (SHRs).

Heart failure: advanced development in genetics and epigenetics.

Heart failure (HF) is a complex pathophysiological syndrome that arises from a primary defect in the ability of the heart to take in and/or eject sufficient blood. Genetic mutations associated with familial dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy can contribute to the various pathologies of HF. Therefore, genetic screening could be an approach for guiding individualized therapies and surveillance.

Lentiviral-mediated silencing of farnesyl pyrophosphate synthase through RNA interference in mice.

Farnesyl pyrophosphate synthase (FPPS) plays a vital role in the mevalonate pathway and has been shown to be involved in hypertrophy and cardiovascular diseases. Lentivirus-mediated RNA interference (RNAi) to knock down a gene of interest has become a promising new tool for the establishment of transgenic animals. The interfering fragment, named pLVT202, was chosen from cardiomyocytes tested in vitro and was microinjected into the perivitelline space of zygotes from C57BL/6J mice via a lentivirus vehicle; 20 were identified as carrying copies of the transgene using the polymerase chain reaction (PCR).

Lycopene protects against apoptosis in hypoxia/reoxygenation‑induced H9C2 myocardioblast cells through increased autophagy.

Lycopene (Ly), the most common type of antioxidant in the majority of diet types, provides tolerance to ischemia/reperfusion injury. However, the underlying mechanism of the protective effects observed following Ly administration remains poorly investigated. The aim of the current study was to investigate whether Ly prevents damage to hypoxia/reoxygenation (HR)‑induced H9C2 myocardioblasts in an autophagy‑dependent manner.

Chronic treatment with qiliqiangxin ameliorates aortic endothelial cell dysfunction in diabetic rats.

Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks.

Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells.

Backgrounds: Autophagy is an important process in the pathogenesis of diabetes and plays a critical role in maintaining cellular homeostasis. However, the autophagic response and its mechanism in diabetic vascular endothelium remain unclear.

Methods And Results: We studied high-glucose-induced renin-angiotensin system (RAS)-mitochondrial damage and its effect on endothelial cells.

Alteration of mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated heart failure with preserved ejection fraction.

Background: Abnormalities of the mevalonate pathway, an important cellular metabolic pathway, are common in many diseases including cardiovascular disease. The mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated diastolic dysfunction remains largely unknown. This study aims to investigate whether the expression of mevalonate pathway related enzyme is altered during the progression of cardiac hypertrophy and associated diastolic dysfunction induced by pressure overload.

Inhibition of farnesyl pyrophosphate synthase prevents norepinephrine-induced fibrotic responses in vascular smooth muscle cells from spontaneously hypertensive rats.

Both norepinephrine (NE) and connective tissue growth factor (CTGF) contribute to vascular fibrosis during hypertension. Recent studies indicate that farnesyl pyrophosphate synthase (FPPS) plays an important role in cardiac remodeling in hypertension. However, the role of FPPS in NE-induced fibrotic responses and related molecular mechanisms is unknown.

Phospholamban antisense RNA improves SR Ca2+-ATPase activity and left ventricular function in STZ-induced diabetic rats.

Objective: To study the effect of phospholamban antisense RNA (asPLB) on sarcoplasmic reticulum Ca2+-ATPase activity and cardiac function in rats with diabetes mellitus (DM) mediated by recombinant adeno-associated virus (rAAV) vector.

Methods: Six weeks after the induction of DM by streptozotocin injected intraperitoneally, the rats were divided into three groups, namely: DM-rAAV-asPLB group, DM-saline group and DM group (control group). The rats in the DM-rAAV-asPLB group were intramyocardially injected with rAAV-asPLB, the rats in the DM-saline group were injected with saline, and those in the control group did not receive any treatment.

Regulation on RhoA in vascular smooth muscle cells under inflammatory stimulation proposes a novel mechanism mediating the multiple-beneficial action of acetylsalicylic acid.

Recent studies have revealed the additional beneficial effects of acetylsalicylic acid (aspirin) in the medication of cardiovascular diseases. The small GTPase RhoA as an important signaling factor is implicated in a wide range of cell functions. This study aimed to investigate the regulatory effect of acetylsalicylic acid on RhoA in vascular smooth muscle cells (VSMCs).

Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats.

Background: Farnesyltransferase (FT), an essential enzyme at the downstream of mevalonate pathway, was reported to be upregulated in hypertrophic cardiomyocytes of spontaneously hypertensive rats (SHRs) compared with myocardium of Wistar-Kyoto rats (WKYs). This upregulation was accompanied with cardiac remodeling. This study was designed to determine whether FT inhibition can alter cardiac remodeling in SHRs.

Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced cardiac hypertrophy and fibrosis in vivo.

Farnesyl pyrophosphate synthase (FPPS), as a key branchpoint of the mevalonate pathway, catalyzes the synthesis of isoprenoid intermediates. The isoprenoid intermediates are needed for protein isoprenylation to participate in cardiac remodeling. We have previously demonstrated that both knockdown of FPPS with small interfering RNA and inhibition of FPPS by alendronate could prevent Ang II-induced hypertrophy in cultured cardiomyocytes.

Cardiac-specific overexpression of farnesyl pyrophosphate synthase induces cardiac hypertrophy and dysfunction in mice.

Aims: Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. In our previous study, we found that inhibition of FPPS attenuates cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and prevents angiotensin (Ang) II-induced hypertrophy in cardiomyocytes. Here, we further investigate the role of FPPS in cardiac hypertrophy and heart failure (HF) using a transgenic (Tg) model, and its mechanisms.