Sex-Specific Disparities in Outcomes of Transcatheter Edge-to-Edge Repair for Mitral Regurgitation: A Multicenter "Real-World" Analysis.

Background: mitral regurgitation (mr) is the most common valvular heart disease (vhd) in the elderly and tends to be more prevalent in women. while relevant sex differences in outcomes are evident in surgically treated collectives, there are very limited and conflicting sex-specific data for the growing cohort of patients undergoing transcatheter edge-to-edge repair (teer).

Objective: to investigate whether sex impacts procedural safety and efficacy, and in-hospital- and long-term outcomes, after teer for mr.

Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc).

Inflammation is a strong driver of atherosclerotic cardiovascular disease (ASCVD). There is a large unmet need for therapies that prevent or reduce excessive inflammation while avoiding systemic immunosuppression. We showed previously that selective inhibition of pro-inflammatory interleukin-6 (IL-6) trans-signalling by the fusion protein olamkicept (sgp130Fc) prevented and reduced experimental murine atherosclerosis in low-density lipoprotein receptor-deficient ( ) mice on a high-fat, high-cholesterol diet independently of low-density lipoprotein (LDL) cholesterol metabolism.

Comparison of Mechanical Support with Impella or Extracorporeal Life Support in Post-Cardiac Arrest Cardiogenic Shock: A Propensity Scoring Matching Analysis.

Our aim was to compare the outcomes of Impella with extracorporeal life support (ECLS) in patients with post-cardiac arrest cardiogenic shock (CS) complicating acute myocardial infarction (AMI). This was a retrospective study of patients resuscitated from out of hospital cardiac arrest (OHCA) with post-cardiac arrest CS following AMI (May 2015 to May 2020). Patients were supported either with Impella 2.

Left Ventricle Architecture and Valvular Integrity Following Microaxial Mechanical Support: A Two-Year Follow-Up Study.

Although the use of microaxilar mechanical circulatory support systems may improve the outcome of patients with cardiogenic shock (CS), little is known about its effect on the long-term structural integrity of left ventricular (LV) valves as well as on the development of LV-architecture. Therefore, we aimed to study the integrity of the LV valves and architecture and function after Impella support. Thus, 84 consecutive patients were monitored over two years having received Impella CP ( = 24) or 2.

Deficiency of Nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 reduces atherosclerosis.

Atherosclerosis is crucially fueled by inflammatory pathways including pattern recognition receptor (PRR)-related signaling of the innate immune system. Currently, the impact of the cytoplasmic PRRs nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2 is incompletely characterized. We, therefore, generated Nod1/Nod2 double knockout mice on a low-density lipoprotein receptor (Ldlr)-deficient background (= LdlrNod1/2) which were subsequently analyzed regarding experimental atherosclerosis, lipid metabolism, insulin resistance and gut microbiota composition.

Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells.

The nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 are mammalian cytosolic pattern recognition receptors sensing bacterial peptidoglycan fragments in order to initiate cytokine expression and pathogen host defense. Since endothelial cells are relevant cells for pathogen recognition at the blood/tissue interface, we here analyzed the role of NOD1- and NOD2-dependently expressed microRNAs (miRNAs, miR) for cytokine regulation in murine pulmonary endothelial cells. The induction of inflammatory cytokines in response to NOD1 and NOD2 was confirmed by increased expression of tumour necrosis factor (Tnf)-α and interleukin (Il)-6.

Suppressor of Cytokine Signaling 1 is Involved in Gene Regulation Which Controls the Survival of Ly6C Monocytes in Mice.

Background/aims: Inflammatory processes are controlled by the fine-tuned balance of monocyte subsets. In mice, different subsets of monocytes can be distinguished by the expression of Ly6C that is highly expressed on inflammatory monocytes (Ly6C) and to a lesser extent on patrolling monocytes (Ly6C). Our previous study revealed an accumulation of Ly6C monocytes in atherosclerotic-prone mice bearing a deficiency in suppressor of cytokine signaling (SOCS)-1 leading to an increased atherosclerotic burden.

Anti-tumor necrosis factor-α therapy increases plaque burden in a mouse model of experimental atherosclerosis.

Background And Aims: Atherosclerosis is critically fueled by vascular inflammation through oxidized lipids and inflammatory cytokines such as tumor necrosis factor (TNF)-α. Genetic disruption of Tnf-α reduces atherosclerosis in experimental mouse models. However, less is known about the therapeutic potential of Tnf-α blockage by pharmacological inhibitors such as monoclonal antibodies, which are already approved for several inflammatory disorders in patients.

NADPH oxidase NOX2 mediates TLR2/6-dependent release of GM-CSF from endothelial cells.

NADPH oxidase-generated reactive oxygen species (ROS) from immune cells are well known to be important for pathogen killing in response to TLR ligands. Here, we investigated a new aspect of NADPH oxidase in the TLR2/6-induced release of the immunologically relevant GM-CSF by endothelial cells. Stimulation of human endothelial cells with TLR2/6 agonist, MALP-2 (macrophage-activating lipopeptide of 2 kDa), induced NADPH oxidase activation and ROS formation.

Targeting Tumor Necrosis Factor-α with Adalimumab: Effects on Endothelial Activation and Monocyte Adhesion.

Objective: It is well known that atherosclerotic inflammatory vascular disease is critically driven by oxidized lipids and cytokines. In this regard, tumor necrosis factor (TNF)-α is known as a crucial mediator of early pro-atherosclerotic events. Epidemiologic data suggest that blockade of TNF-α has beneficial effects on vascular outcomes in patients with rheumatoid arthritis, however, detailed mechanistic studies are still lacking.

Lipocalin (LCN) 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease.

Background: Lipocalin (LCN) 2 is associated with multiple acute and chronic inflammatory diseases but the underlying molecular and cellular mechanisms remain unclear. Here, we investigated whether LCN2 is released from macrophages and contributes to pro-atherosclerotic processes and whether LCN2 plasma levels are associated with the severity of coronary artery disease progression in humans.

Methods And Results: In an autocrine-paracrine loop, tumor necrosis factor (TNF)-α promoted the release of LCN2 from murine bone-marrow derived macrophages (BMDM) and vice versa.

Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition.

Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined.

Toll-like receptor 2/6 agonist macrophage-activating lipopeptide-2 promotes reendothelialization and inhibits neointima formation after vascular injury.

Objective: Reendothelialization after vascular injury (ie, balloon angioplasty or stent implantation) is clinically extremely relevant to promote vascular healing. We here investigated the therapeutic potential of the toll-like receptor 2/6 agonist macrophage-activating lipopeptide (MALP)-2 on reendothelialization and neointima formation in a murine model of vascular injury.

Approach And Results: The left common carotid artery was electrically injured, and reendothelialization was quantified by Evans blue staining after 3 days.

Experimental gingivitis induces systemic inflammatory markers in young healthy individuals: a single-subject interventional study.

Objectives: We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development.

Background: Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown.

Role of suppressor of cytokine signaling-1 in murine atherosclerosis.

Background: While the impact of inflammation as the substantial driving force of atherosclerosis has been investigated in detail throughout the years, the influence of negative regulators of pro-atherogenic pathways on plaque development has remained largely unknown. Suppressor of cytokine signaling (SOCS)-1 potently restricts transduction of various inflammatory signals and, thereby modulates T-cell development, macrophage activation and dendritic cell maturation. Its role in atherogenesis, however has not been elucidated so far.

Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice.

Background: Symmetrical dimethylarginine (SDMA), the structural isomer of the nitric oxide synthase inhibitor asymmetrical dimethylarginine, has long been regarded as an inert substance. Recent epidemiological and preclinical data suggest that it might be involved in the pathophysiology of renal and cardiovascular diseases. Therefore, we aimed to investigate the effect of chronic SDMA infusion on renal and cardiac function in mice.

Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice.

Objective: Transsignaling of interleukin (IL)-6 is a central pathway in the pathogenesis of disorders associated with chronic inflammation, such as Crohn disease, rheumatoid arthritis, and inflammatory colon cancer. Notably, IL-6 also represents an independent risk factor for coronary artery disease (CAD) in humans and is crucially involved in vascular inflammatory processes.

Methods And Results: In the present study, we showed that treatment with a fusion protein of the natural IL-6 transsignaling inhibitor soluble glycoprotein 130 (sgp130) and IgG1-Fc (sgp130Fc) dramatically reduced atherosclerosis in hypercholesterolemic Ldlr(-/-) mice without affecting weight gain and serum lipid levels.

Chemokine receptor 7 knockout attenuates atherosclerotic plaque development.

Background: Atherosclerosis is a systemic inflammatory disease characterized by the formation of atherosclerotic plaques. Both innate immunity and adaptive immunity contribute to atherogenesis, but the mode of interaction is poorly understood. Chemokine receptor 7 (CCR7) is critically involved in the transition from innate to adaptive immune activation by coordinating the migration to and positioning of antigen-presenting dendritic cells and T cells in secondary lymphoid organs.

Toll-like receptor 2/6 stimulation promotes angiogenesis via GM-CSF as a potential strategy for immune defense and tissue regeneration.

Toll-like receptors (TLRs) are known primarily as pathogen recognition receptors of the innate immunity, initiating inflammatory pathways to organize the immune defense. More recently, an involvement of TLRs in various physiologic and pathologic processes has been reported. Because many of these processes implicate angiogenesis, we here elucidated the role of a TLR2/6-dependent pathway on angiogenesis using the TLR2/6 agonist macrophage-activating lipopeptide of 2 kDa (MALP-2), a common bacterial lipopeptide.

Hepatocyte gp130 deficiency reduces vascular remodeling after carotid artery ligation.

Inflammation and vascular remodeling are hallmarks of atherosclerosis, hypertension, and restenosis after angioplasty. Here we investigated the role of the hepatocyte gp130-dependent systemic acute phase response on vascular remodeling after carotid artery ligation. Mice with a hepatocyte-specific gp130 knockout on an apolipoprotein E(-/-) background (gp130-) were compared with control mice (gp130(flox)).

How much is too much? Interleukin-6 and its signalling in atherosclerosis.

The importance of inflammation as a driver of pathology is no longer confined to autoimmune and infectious diseases. In line with convincing experimental data as well as abundant clinical findings the current view of atherosclerosis points to inflammation as a critical regulator of atherosclerotic plaque formation and progression leading to the fatal clinical endpoints myocardial infarction, stroke or sudden cardiac death. The underlying mechanisms have been a matter of intense research during the last decades.

NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice.

The trigger for liver regeneration, including shear stress, has been the subject of ongoing debate. Blood vessel-derived gaseous molecules carbon monoxide (CO) and nitric oxide (NO) regulate vascular tone and play an important role in liver regeneration. In heme oxygenase-1 (HO-1) transgenic mice, it has been shown that CO-mediated impairment of vasorelaxation is an NO-dependent event.

Inhibition of heme oxygenase-1 protects against tissue injury in carbon tetrachloride exposed livers.

Background/aims: During the metabolism of the hepatotoxin carbon tetrachloride (CCl(4)) by cytochrome P450, heme, and free radicals are released. Heme oxygenase (HO-1) is an enzyme that is induced by heme as well as oxidative stress and has been reported to be involved in mediating protection against toxic liver injury. The purpose of the present study was to specify the role of HO-1 in CCl(4)-hepatotoxicity.

Pifithrin-alpha induced p53 inhibition does not affect liver regeneration after partial hepatectomy in mice.

Background/aims: Beside its well-known function as tumour suppressor gene, p53 is supposed to positively regulate cell division and cell differentiation. Because hepatocyte proliferation has been reported to be reduced by blockade of p53 function in vitro, we examined in the present study the impact of p53 inhibition on hepatocyte proliferation in vivo.

Methods: Mice treated with either pifithrin-alpha (PFT), a p53-inactivating agent, or the equivalent volume of vehicle, were subjected to 70% hepatectomy.