Bone marrow-derived na ïve B lymphocytes improve heart function after myocardial infarction: a novel cardioprotective mechanism for empagliflozin
AbstractThe role of adaptive immunity in myocardial recovery post myocardial infarction (MI), particularly the immune response by B lymphocytes, remains elusive. Bone marrow immune microenvironment in response to MI is remotely regulated by the hypothalamic pituitary adrenal (HPA) axis. We utilized the cardioprotective actions of SGLT2 inhibitor to identify and characterize bone marrow B cell subsets that respond to myocardial injury. Initially, we preformed ligation of left anterior descendant (LAD) coronary artery in male C57BL/6J mice to monitor the dynamic changes of immune cells across tissues. Mechanistic insights fr...
Source: Basic Research in Cardiology - September 28, 2022 Category: Cardiology Source Type: research
Erythrocytes from patients with ST-elevation myocardial infarction induce cardioprotection through the purinergic P2Y13 receptor and nitric oxide signaling
This study demonstrates a novel function of RBCs in STEMI patients providing protection against myocardial ischemia–reperfusion injury through the P2Y13 receptor and the NO –sGC–PKG pathway. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - September 16, 2022 Category: Cardiology Source Type: research
Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions
AbstractTachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits. Tachypacing was performed with 330 bpm for 10 days (n = 11, early left ventricular dysfunction) or with up to 380 bpm over 30 days (n = 24, tachycardiomyopathy, TCM). Inn = 26, pacemakers remained inactive (SHAM). Left ventricular tissue was subjected to respirometry, metabolomics and acetylomics. Results wer...
Source: Basic Research in Cardiology - September 6, 2022 Category: Cardiology Source Type: research
Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality
AbstractMyocardial infarction (MI) with subsequent depression is associated with increased cardiac mortality. Impaired central mineralocorticoid (MR) and glucocorticoid receptor (GR) equilibrium has been suggested as a key mechanism in the pathogenesis of human depression. Here, we investigate if deficient central MR/GR signaling is causative for a poor outcome after MI in mice. Mice with an inducible forebrain-specific MR/GR knockout (MR/GR-KO) underwent baseline and follow-up echocardiography every 2 weeks after MI or sham operation. Behavioral testing at 4 weeks confirmed significant depressive-like behavior and, str...
Source: Basic Research in Cardiology - September 6, 2022 Category: Cardiology Source Type: research
Acid sphingomyelinase deactivation post-ischemia promotes brain angiogenesis and remodeling by small extracellular vesicles
AbstractAntidepressants have been reported to enhance stroke recovery independent of the presence of depressive symptoms. They have recently been proposed to exert their mood-stabilizing actions by inhibition of acid sphingomyelinase (ASM), which catalyzes the hydrolysis of sphingomyelin to ceramide. Their restorative action post-ischemia/reperfusion (I/R) still had to be defined. Mice subjected to middle cerebral artery occlusion or cerebral microvascular endothelial cells exposed to oxygen –glucose deprivation were treated with vehicle or with the chemically and pharmacologically distinct antidepressants amitriptyline,...
Source: Basic Research in Cardiology - August 29, 2022 Category: Cardiology Source Type: research
Extracellular stiffness induces contractile dysfunction in adult cardiomyocytes via cell-autonomous and microtubule-dependent mechanisms
AbstractThe mechanical environment of the myocardium has a potent effect on cardiomyocyte form and function, yet an understanding of the cardiomyocyte responses to extracellular stiffening remains incomplete. We therefore employed a cell culture substrate with tunable stiffness to define the cardiomyocyte responses to clinically relevant stiffness increments in the absence of cell –cell interactions. When cultured on substrates magnetically actuated to mimic the stiffness of diseased myocardium, isolated rat adult cardiomyocytes exhibited a time-dependent reduction of sarcomere shortening, characterized by slowed contrac...
Source: Basic Research in Cardiology - August 25, 2022 Category: Cardiology Source Type: research
Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
In this study, we aimed to assess its effects on cardiac sympathetic innervation and metabolism. Transient myocardial ischemia is induced by ligature of the left anterior descending coronary artery (LAD) in male Sprague –Dawley rats, and in vivo cardiac 2-[18F]FDG and [11C]mHED PET scans were performed at 14 –15 days after ischemia. RIPerc was induced by three cycles of 5-min-long unilateral hind limb ischemia and intermittent 5 min of reperfusion during LAD occlusion period. The PET quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional ra dioactive quantif...
Source: Basic Research in Cardiology - August 25, 2022 Category: Cardiology Source Type: research
Mitochondrial calpain-1 activates NLRP3 inflammasome by cleaving ATP5A1 and inducing mitochondrial ROS in CVB3-induced myocarditis
In conclusion, CVB3 infection induced calpain-1 accum ulation in mitochondria, and led to subsequent ATP5A1 cleavage, mitochondrial ROS overproduction, and impaired mitochondrial function, eventually causing NLRP3 inflammasome activation and inducing pyroptosis. Therefore, our findings established the role of calpain in viral myocarditis and unveiled i ts underlying mechanism of its action. Calpain appears as a promising target for the treatment of viral myocarditis. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - August 23, 2022 Category: Cardiology Source Type: research
Remote ischaemic conditioning: defining critical criteria for success —report from the 11th Hatter Cardiovascular Workshop
Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the pote ntial for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify...
Source: Basic Research in Cardiology - August 15, 2022 Category: Cardiology Source Type: research
Myeloid leukocytes ’ diverse effects on cardiovascular and systemic inflammation in chronic kidney disease
AbstractChronic kidney disease ’s prevalence rises globally. Whereas dialysis treatment replaces the kidney’s filtering function and prolongs life, dreaded consequences in remote organs develop inevitably over time. Even milder reductions in kidney function not requiring replacement therapy associate with bacterial infections , cardiovascular and heart valve disease, which markedly limit prognosis in these patients. The array of complications is diverse and engages a wide gamut of cellular and molecular mechanisms. The innate immune system is profoundly and systemically altered in chronic kidney disease and, as a unify...
Source: Basic Research in Cardiology - July 27, 2022 Category: Cardiology Source Type: research
Monoamine oxidase A and organic cation transporter 3 coordinate intracellular β1AR signaling to calibrate cardiac contractile function
AbstractWe have recently identified a pool of intracellular β1 adrenergic receptors ( β1ARs) at the sarcoplasmic reticulum (SR) crucial for cardiac function. Here, we aim to characterize the integrative control of intracellular catecholamine for subcellular β1AR signaling and cardiac function. Using anchored F örster resonance energy transfer (FRET) biosensors and transgenic mice, we determined the regulation of compartmentalized β1AR-PKA signaling at the SR and plasma membrane (PM) microdomains by organic cation transporter 3 (OCT3) and monoamine oxidase A (MAO-A), two critical modulators of catecholamine uptake and ...
Source: Basic Research in Cardiology - July 17, 2022 Category: Cardiology Source Type: research
Renal denervation reduces atrial remodeling in hypertensive rats with metabolic syndrome
In conclusion, suppression of renal sympathetic nerve activity by RDN prevents atrial remodeling in metabolic syndrome by reducing atrial sympathetic innervation and by modulating RAGE/sRAGE balance and reducing pro-inflammatory and pro-fibrotic RAGE ligands, which provides a potential therapeutic mechanism to reduce the development of AF. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - July 14, 2022 Category: Cardiology Source Type: research
Why is endothelial resilience key to maintain cardiac health?
AbstractMyocardial injury as induced by myocardial infarction results in tissue ischemia, which critically incepts cardiomyocyte death. Endothelial cells play a crucial role in restoring oxygen and nutrient supply to the heart. Latest advances in single-cell multi-omics, together with genetic lineage tracing, reveal a transcriptional and phenotypical adaptation to the injured microenvironment, which includes alterations in metabolic, mesenchymal, hematopoietic and pro-inflammatory signatures. The extent of transition in mesenchymal or hematopoietic cell lineages is still debated, but it is clear that several of the adaptiv...
Source: Basic Research in Cardiology - July 14, 2022 Category: Cardiology Source Type: research
