Low-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload.

Pressure overload induces pathological cardiac remodeling, including cardiac hypertrophy and fibrosis, resulting in cardiac dysfunction or heart failure. Recently, we observed that the low-density lipoprotein receptor-related protein 6 (LRP6), has shown potential in enhancing cardiac function by mitigating cardiac fibrosis in a mouse model subjected to pressure overload. In this study, we investigated the role of LRP6 as a potential modulator of pressure overload-induced cardiac hypertrophy and elucidated the underlying molecular mechanisms.

Bufalin Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Macrophage Pyroptosis via P62 Pathway.

Bufalin, which is isolated from toad venom, exerts positive effects on hearts under pathological circumstance. We aimed to investigate the effects and mechanisms of bufalin on myocardial I/R injury. In vivo, bufalin ameliorated myocardial I/R injury, which characteristics with better ejection function, decreased infarct size and less apoptosis.

The polycomb protein complex interacts with GATA-6/PPARα to inhibit α-MHC expression.

Transcription factors collaborate with epigenetic regulatory factors to orchestrate cardiac differentiation for heart development, but the underlying mechanism is not fully understood. Here, we report that GATA-6 induces cardiac differentiation but peroxisome proliferator-activated receptor α (PPARα) reverses GATA-6-induced cardiac differentiation, possibly because GATA-6/PPARα recruits the polycomb protein complex containing EZH2/Ring1b/BMI1 to the promoter of the cardiac-specific α-myosin heavy chain (α-MHC) gene and suppresses α-MHC expression, which ultimately inhibits cardiac differentiation. Furthermore, Ring1b ubiquitylates PPARα and GATA-6.

Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure.

Sustained myocardial hypertrophy or left ventricular hypertrophy (LVH) triggered by pressure overload is strongly linked to adverse cardiovascular outcomes. Here, we investigated the clinical relationship between serum HSP90α (an isoform of HSP90) levels and LVH in patients with hypertension or aortic stenosis (AS) and explored underlying mechanisms in pressure overload mouse model. We built a pressure overload mouse model via transverse aortic constriction (TAC).

Association of serum iron with all-cause mortality and cardiovascular mortality in the cardiovascular patients: a retrospective cohort study based on the NHANES 1999-2018.

Background: Cardiovascular disease (CVD) is one of the leading global causes of death, and serum iron (SI) levels may be associated with the mortality of CVD. However, there is still a knowledge gap regarding the relationship between SI and mortality in the CVD population.

Methods: An analysis was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018.

ORP5 promotes cardiac hypertrophy by regulating the activation of mTORC1 on lysosome.

Introduction: Oxysterol binding protein (OSBP)-related protein 5 (ORP5) mainly functions as a lipid transfer protein at membrane contact sites (MCS). ORP5 facilitates cell proliferation through the activation of mTORC1 signaling. While the pro-hypertrophic effects of mTORC1 are well-documented, the specific role of ORP5 in the context of pathological cardiac hypertrophy remains inadequately understood.

Bruton tyrosine kinase promotes wound healing after myocardial infarction by inhibiting the transcription of u-PA.

Backgrounds: Bruton tyrosine kinase (BTK), which is highly expressed in immune cells, plays a critical role in regulating the function of macrophages. A growing body of evidence has demonstrated that the accumulation of macrophages in cardiac tissue after myocardial infarction (MI) significantly affects wound healing and ventricular remodeling during the early phase of repair after MI. However, the role of BTK in cardiac repair post-MI, especially in macrophage-mediated repair, remains unclear.

A Novel Method for Mitochondrial Membrane Potential Detection in Heart Tissue Following Ischemia-reperfusion in Mice.

Objective: Myocardial ischemia-reperfusion (I/R) injury is associated with a significant reduction in the mitochondrial membrane potential (MMP, ΔΨm). Fluorescence-based assays are effective for labelling active mitochondria in living cells; their application in heart tissue, however, represents a challenge because of a low yield of viable cardiomyocytes after cardiac perfusion. This study aimed to examine a novel method for detecting the changes in the MMP of mouse heart tissue following I/R injury.

oG-miR-6513-5p/BCL2L13 Axis Regulates Mitophagy during Oxidative Stress in the Human Saphenous Vein Endothelial Cells.

Venous graft decay (VGD) occurs in coronary artery bypass grafting (CABG), and ischemia-reperfusion oxidative stress injury during the operation is involved in VGD. To explore the cellular phenotypic changes during this process, a stable oxidative stress model of human saphenous vein endothelial cells (HSVECs) is constructed. Through proteomics and cell experiments, it is found that the expression of BCL2L13 is upregulated during oxidative stress of HSVECs, and BCL2L13 regulated mitophagy through receptor-mediated interaction with LC3 and plays a role in cell protection.

Integrative proteomic and metabolomic elucidation of cardiomyopathy with in vivo and in vitro models and clinical samples.

Cardiomyopathy is a prevalent cardiovascular disease that affects individuals of all ages and can lead to life-threatening heart failure. Despite its variety in types, each with distinct characteristics and causes, our understanding of cardiomyopathy at a systematic biology level remains incomplete. Mass spectrometry-based techniques have emerged as powerful tools, providing a comprehensive view of the molecular landscape and aiding in the discovery of biomarkers and elucidation of mechanisms.

Single-Cell Time-Resolved Metabolomics and Lipidomics Reveal Apoptotic and Ferroptotic Heterogeneity during Foam Cell Formation.

Macrophage-derived foam cells play a crucial role in plaque formation and rupture during the progression of atherosclerosis. Traditional studies have often overlooked the heterogeneity of foam cells, focusing instead on populations of cells. To address this, we have developed time-resolved, single-cell metabolomics and lipidomics approaches to explore the heterogeneity of macrophages during foam cell formation.

Engineered mouse H1 promoter mutants with superior RNA polymerase III activity.

Vectors incorporating the human H1 (hH1) promoter are being applied for RNA interference (RNAi) experiments and genome editing. Although extensive studies have been conducted on the hH1 promoter, our understanding of the mouse H1 promoter remains limited. In this study, we predicted the 163 bp mouse H1 (mH1) promoter and 84 bp mouse H1 core (mH1 core) promoter through global alignment and detected its RNA polymerase II (Pol II) and III activities through the expression of the EGFP and the abundance of artificial sequence, which were generally slightly weaker than those of the hH1 promoter.

Increased Secreted Frizzled-Related Protein 2 in Hypertension-Induced Left Ventricular Remodeling.

Background: Secreted frizzled-related protein 2 (sFRP2) is involved in various cardiovascular diseases. However, its relevance in left ventricular (LV) remodeling in patients with hypertension (HTN) is obscure.

Methods: In this study, 196 patients with HTN were included, 59 with echocardiographic LV remodeling.

RBM15 Protects From Myocardial Infarction by Stabilizing NAE1.

RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15-an important RNA-binding protein and a significant regulator of RNA methylation-in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI).

Blocking HR signal aggravates atherosclerosis by promoting inflammation and foam cell formation.

Atherosclerosis (AS) is a chronic inflammatory arterial disease, in which abnormal lipid metabolism and foam cell formation play key roles. Histamine is a vital biogenic amine catalyzed by histidine decarboxylase (HDC) from L-histidine. Histamine H1 receptor (HR) antagonist is a commonly encountered anti-allergic agent in the clinic.

Heavy Metal Scavenger Metallothionein Rescues Against Cold Stress-Evoked Myocardial Contractile Anomalies Through Regulation of Mitophagy.

Cold stress prompts an increased prevalence of cardiovascular morbidity yet the underneath machinery remains unclear. Oxidative stress and autophagy appear to contribute to cold stress-induced cardiac anomalies. Our present study evaluated the effect of heavy metal antioxidant metallothionein on cold stress (4 °C)-induced in cardiac remodeling and contractile anomalies and cell signaling involved including regulation of autophagy and mitophagy.

TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy.

A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.

Role of Lymphangiogenesis in Cardiac Repair and Regeneration.

This article highlights the importance of the structure and function of cardiac lymphatics in cardiovascular diseases and the therapeutic potential of cardiac lymphangiogenesis. Specifically, we explore the innate lymphangiogenic response to damaged cardiac tissue or cardiac injury, derive key findings from regenerative models demonstrating how robust lymphangiogenic responses can be supported to improve cardiac function, and introduce an approach to imaging the structure and function of cardiac lymphatics.

Apelin receptor inhibition in ischemia-reperfused mouse hearts protected by endogenous n-3 polyunsaturated fatty acids.

While the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on cardiac ischemia-reperfusion (IR) injury have been previously reported, limited data are available regarding how these fatty acids affect membrane receptors and their downstream signaling following IR injury. We aimed to identify potential receptors activated by n-3 PUFAs in IR hearts to understand the regulatory mechanisms of these receptors. We used mice, which naturally have elevated levels of n-3 PUFAs, and C57BL/6J mice as a control group to create a myocardial IR injury model through Langendorff perfusion.

Mitochondrial transplantation ameliorates doxorubicin-induced cardiac dysfunction via activating glutamine metabolism.

Doxorubicin is a wildly used effective anticancer agent. However, doxorubicin use is also related to cardiotoxic side effect in some patients. Mitochondrial damage has been shown to be one of the pathogeneses of doxorubicin-induced myocardial injury.

Accumulation of endogenous adenosine improves cardiomyocyte metabolism via epigenetic reprogramming in an ischemia-reperfusion model.

Adenosine kinase (ADK) plays the major role in cardiac adenosine metabolism, so that inhibition of ADK increases myocardial adenosine levels. While the cardioprotective actions of extracellular adenosine against ischemia/reperfusion (I/R) are well-established, the role of cellular adenosine in protection against I/R remains unknown. Here we investigated the role of cellular adenosine in epigenetic regulation on cardiomyocyte gene expression, glucose metabolism and tolerance to I/R.

Inhibition of GSDMD activation by Z-LLSD-FMK or Z-YVAD-FMK reduces vascular inflammation and atherosclerotic lesion development in ApoE mice.

Pyroptosis is a form of pro-inflammatory cell death that can be mediated by gasdermin D (GSDMD) activation induced by inflammatory caspases such as caspase-1. Emerging evidence suggests that targeting GSDMD activation or pyroptosis may facilitate the reduction of vascular inflammation and atherosclerotic lesion development. The current study investigated the therapeutic effects of inhibition of GSDMD activation by the novel GSDMD inhibitor N-Benzyloxycarbonyl-Leu-Leu-Ser-Asp(OMe)-fluoromethylketone (Z-LLSD-FMK), the specific caspase-1 inhibitor N-Benzyloxycarbonyl-Tyr-Val-Ala-Asp(OMe)-fluoromethylketone (Z-YVAD-FMK), and a combination of both on atherosclerosis in ApoE mice fed a western diet at 5 weeks of age, and further determined the efficacy of these polypeptide inhibitors in bone marrow-derived macrophages (BMDMs).