Dapagliflozin and atrial fibrillation: elevated dosing to achieve class I antiarrhythmic effects?
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 3, 2024 Category: Cardiology Source Type: research
Exercise training decreases lactylation and prevents myocardial ischemia –reperfusion injury by inhibiting YTHDF2
AbstractExercise improves cardiac function and metabolism. Although long-term exercise leads to circulating and micro-environmental metabolic changes, the effect of exercise on protein post-translational lactylation modifications as well as its functional relevance is unclear. Here, we report that lactate can regulate cardiomyocyte changes by improving protein lactylation levels and elevating intracellular N6-methyladenosine RNA-binding protein YTHDF2. The intrinsic disorder region of YTHDF2 but not the RNA m6A-binding activity is indispensable for its regulatory function in influencing cardiomyocyte cell size changes and ...
Source: Basic Research in Cardiology - April 2, 2024 Category: Cardiology Source Type: research
Role of inflammatory signaling pathways involving the CD40 –CD40L–TRAF cascade in diabetes and hypertension—insights from animal and human studies
AbstractCD40L –CD40–TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L–CD40–TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipi demia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L–CD4...
Source: Basic Research in Cardiology - March 30, 2024 Category: Cardiology Source Type: research
Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation
AbstractRight ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magn...
Source: Basic Research in Cardiology - March 27, 2024 Category: Cardiology Source Type: research
Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside
AbstractDecreased nicotinamide adenine dinucleotide (NAD+) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia –reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD+ precursor due to efficient NAD+ elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown. Furthermore, the influence of insulin, a known modulator of cardioprotective efficacy, on the protective effects of NR has n...
Source: Basic Research in Cardiology - March 25, 2024 Category: Cardiology Source Type: research
Early microvascular coronary endothelial dysfunction precedes pembrolizumab-induced cardiotoxicity. Preventive role of high dose of atorvastatin
AbstractImmune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vitro and pembrolizumab ’s (Pem’s) cardiotoxicity in vivo, seeking for translational prevention means. Cytotoxicity was investigated in primary cardiomyocytes and splenocytes, incubated with ipilimumab, Pem and avelumab. Pem’s cross-reactivity was assessed by circular dichroism (CD) on biotechnologically produced hum an and murine PD-1 and in silico. C57BL6/J male mice received IgG4 or Pem for 2 ...
Source: Basic Research in Cardiology - March 23, 2024 Category: Cardiology Source Type: research
Identification of a mechanism promoting mitochondrial sterol accumulation during myocardial ischemia –reperfusion: role of TSPO and STAR
This study reveals a novel mitochondrial interaction between TSPO and STAR to promote cholesterol and deleterious sterol mitochondrial accumulation during myocardial ischemia–reperfusion. This interaction regulates mitochondrial homeostasis and plays a key role during mitochond rial injury. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 22, 2024 Category: Cardiology Source Type: research
Oxidation –reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium
In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estim ating the size of the MI during early phases of reperfusion. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 18, 2024 Category: Cardiology Source Type: research
Characterizing the immune response to myocardial infarction in pigs
AbstractThough myocardial infarction (MI) in pigs is a well-established translational large animal model, it has not yet been widely used for immunotherapy studies, and a comprehensive description of the immune response to MI in this species is lacking. We induced MI in Landrace pigs by balloon occlusion of the left anterior descending artery over 90 min. Within 14 days, the necrotic myocardium was progressively replaced by scar tissue with involvement of myofibroblasts. We characterized the immune response in the heart ex vivo by (immuno)histology, flow cytometry, and RNA sequencing of myocardial tissue on days 3, 7, a...
Source: Basic Research in Cardiology - March 15, 2024 Category: Cardiology Source Type: research
Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging
This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX;n = 16) for induction of AIC or saline as corresponding control (n = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (n = 8 per group) were scanned ex vivo by high-resolution DTI at 7 T. Results were correlated with histopathology and mass spectrometry imaging. Mice with AIC demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 ± 6%,P < 0.001), impaired global longitudinal strain (−19.6 ±...
Source: Basic Research in Cardiology - March 14, 2024 Category: Cardiology Source Type: research
Pathophysiology and clinical relevance of atrial myopathy
AbstractAtrial myopathy is a condition that consists of electrical, structural, contractile, and autonomic remodeling of the atria and is the substrate for development of atrial fibrillation, the most common arrhythmia. Pathophysiologic mechanisms driving atrial myopathy are inflammation, oxidative stress, atrial stretch, and neurohormonal signals, e.g., angiotensin-II and aldosterone. These mechanisms initiate the structural and functional remodeling of the atrial myocardium. Novel therapeutic strategies are being developed that target the pathophysiologic mechanisms of atrial myopathy. In this review, we will discuss the...
Source: Basic Research in Cardiology - March 12, 2024 Category: Cardiology Source Type: research
Role of CD4+ T-cells for regulating splenic myelopoiesis and monocyte differentiation after experimental myocardial infarction
AbstractMyocardial infarction (MI) induces the generation of proinflammatory Ly6Chigh monocytes in the spleen and the recruitment of these cells to the myocardium. CD4+ Foxp3+ CD25+ T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4+ T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4+ T-cell deficient animals. Conventional CD4+ T-cells promoted myelopoiesis in vitro by ce...
Source: Basic Research in Cardiology - March 4, 2024 Category: Cardiology Source Type: research
Crosstalk of human coronary perivascular adipose-derived stem cells with vascular cells: role of tissue factor
AbstractThe coronary perivascular adipose tissue (cPVAT) has been associated to the burden of cardiovascular risk factors and to the underlying vessel atherosclerotic plaque severity. Although the “outside to inside” hypothesis of PVAT-derived-adipokine regulation of vessel function is currently accepted, whether the resident mesenchymal stem cells (ASCs) in PVAT have a regulatory role on the underlying vascular arterial smooth muscle cells (VSMCs) is not known. Here, we investigated the interactions between resident PVAT-ASCs and VSMCs. ASCs were obtained from PVAT overlying the left anterior descending (LAD) coronary...
Source: Basic Research in Cardiology - March 2, 2024 Category: Cardiology Source Type: research
