In-ovo echocardiography for application in cardiovascular research
In conclusion,in-ovo echocardiography is a feasible alternative tool forbasic cardiovascular research, which can easily be implemented into the small animal research environment using existing infrastructure to replace mice and rat experiments, and thus, reduce use of laboratory animals according to the 3R principle. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - May 16, 2023 Category: Cardiology Source Type: research
Matrix metalloproteinases in coronary artery disease and myocardial infarction
AbstractCardiovascular diseases (CVDs) remain the leading cause of death worldwide. Most cardiovascular deaths are caused by ischaemic heart diseases such as myocardial infarction (MI). Hereby atherosclerosis in the coronary arteries often precedes disease manifestation. Since tissue remodelling plays an important role in the development and progression of atherosclerosis as well as in outcome after MI, regulation of matrix metalloproteinases (MMPs) as the major ECM-degrading enzymes with diverse other functions is crucial. Here, we provide an overview of the expression profiles of MMPs in coronary artery and left ventricu...
Source: Basic Research in Cardiology - May 9, 2023 Category: Cardiology Source Type: research
Multilineage contribution of CD34+ cells in cardiac remodeling after ischemia/reperfusion injury
This study aimed to delineate the biological functions of heterogenous CD34+ cell populations and investigate the net effect of CD34+ cell intervention on cardiac remodeling. We confirmed, by combining single-cell RNA sequencing on human and mouse ischemic hearts and an inducibleCd34 lineage-tracing mouse model, thatCd34+ cells mainly contributed to the commitment of mesenchymal cells, endothelial cells (ECs), and monocytes/macrophages during heart remodeling with distinct pathological functions. TheCd34+-lineage-activated mesenchymal cells were responsible for cardiac fibrosis, while CD34+Sca-1high was an active precursor...
Source: Basic Research in Cardiology - May 5, 2023 Category: Cardiology Source Type: research
Integration of epigenetic regulatory mechanisms in heart failure
AbstractThe number of “omics” approaches is continuously growing. Among others, epigenetics has appeared as an attractive area of investigation by the cardiovascular research community, notably considering its association with disease development. Complex diseases such as cardiovascular diseases have to be tackled us ing methods integrating different omics levels, so called “multi-omics” approaches. These approaches combine and co-analyze different levels of disease regulation. In this review, we present and discuss the role of epigenetic mechanisms in regulating gene expression and provide an integrated vie w of h...
Source: Basic Research in Cardiology - May 4, 2023 Category: Cardiology Source Type: research
Sexual dimorphism in bidirectional SR-mitochondria crosstalk in ventricular cardiomyocytes
AbstractCalcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca2+ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca2+] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca2+ accumulation, thereby reducing ROS production and stress-induced intracellular Ca2+ mishandling. Ex...
Source: Basic Research in Cardiology - May 3, 2023 Category: Cardiology Source Type: research
Electrophysiological and calcium-handling development during long-term culture of human-induced pluripotent stem cell-derived cardiomyocytes
In this study, we identify, track and model the dynamic developmental behaviour of key ionic currents and Ca2+-handling properties in hiPSC-CM over long-term culture (30 –80 days). hiPSC-CMs > 50 days post differentiation show significantly largerICa,L density along with an increasedICa,L-triggered Ca2+-transient.INa andIK1 densities significantly increase in late-stage cells, contributing to increased upstroke velocity and reduced action potential duration, respectively. Importantly, our in silico model of hiPSC-CM electrophysiological age dependence confirmedIK1 as the key ionic determinant of action potentia...
Source: Basic Research in Cardiology - April 5, 2023 Category: Cardiology Source Type: research
Membrane remodelling triggers maturation of excitation –contraction coupling in 3D-shaped human-induced pluripotent stem cell-derived cardiomyocytes
AbstractThe prospective use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for cardiac regenerative medicine strongly depends on the electro-mechanical properties of these cells, especially regarding the Ca2+-dependent excitation –contraction (EC) coupling mechanism. Currently, the immature structural and functional features of hiPSC-CM limit the progression towards clinical applications. Here, we show that a specific microarchitecture is essential for functional maturation of hiPSC-CM. Structural remodelling towards a cub oid cell shape and induction of BIN1, a facilitator of membrane invaginat...
Source: Basic Research in Cardiology - March 29, 2023 Category: Cardiology Source Type: research
Multi-omic analysis of the cardiac cellulome defines a vascular contribution to cardiac diastolic dysfunction in obese female mice
AbstractCoronary microvascular dysfunction (CMD) is associated with cardiac dysfunction and predictive of cardiac mortality in obesity, especially in females. Clinical data further support that CMD associates with development of heart failure with preserved ejection fraction and that mineralocorticoid receptor (MR) antagonism may be more efficacious in obese female, versus male, HFpEF patients. Accordingly, we examined the impact of smooth muscle cell (SMC)-specific MR deletion on obesity-associated coronary and cardiac diastolic dysfunction in female mice. Obesity was induced in female mice via western diet (WD) feeding a...
Source: Basic Research in Cardiology - March 29, 2023 Category: Cardiology Source Type: research
Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure
This study interrogated the local metabolic hypothesis of autoregulation by testing the hypothesis that hypoxemia-induced exaggeration of the metabolic error signal improves the autoregulatory response. Experiments were performed on open-chest anesthetized swine during stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg under normoxic (n = 15) and hypoxemic (n = 8) conditions, in the absence and presence of dobutamine-induced increases in myocardial oxygen consumption (MVO2) (n = 5–7). Hypoxemia (PaO2 < 40 mmHg) decreased coronary venous PO2 (CvPO2) ~ 30% (P < 0....
Source: Basic Research in Cardiology - March 29, 2023 Category: Cardiology Source Type: research
Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure
AbstractPrecision-based molecular phenotyping of heart failure must overcome limited access to cardiac tissue. Although epigenetic alterations have been found to underlie pathological cardiac gene dysregulation, the clinical utility of myocardial epigenomics remains narrow owing to limited clinical access to tissue. Therefore, the current study determined whether patient plasma confers indirect phenotypic, transcriptional, and/or epigenetic alterations to ex vivo cardiomyocytes to mirror the failing human myocardium. Neonatal rat ventricular myocytes (NRVMs) and single-origin human induced pluripotent stem cell-derived car...
Source: Basic Research in Cardiology - March 20, 2023 Category: Cardiology Source Type: research
A cardiologist ’s guide to machine learning in cardiovascular disease prognosis prediction
AbstractA modern-day physician is faced with a vast abundance of clinical and scientific data, by far surpassing the capabilities of the human mind. Until the last decade, advances in data availability have not been accompanied by analytical approaches. The advent of machine learning (ML) algorithms might improve the interpretation of complex data and should help to translate the near endless amount of data into clinical decision-making. ML has become part of our everyday practice and might even further change modern-day medicine. It is important to acknowledge the role of ML in prognosis prediction of cardiovascular dis...
Source: Basic Research in Cardiology - March 20, 2023 Category: Cardiology Source Type: research
Ploidy-stratified single cardiomyocyte transcriptomics map Zinc Finger E-Box Binding Homeobox 1 to underly cardiomyocyte proliferation before birth
AbstractWhereas cardiomyocytes (CMs) in the fetal heart divide, postnatal CMs fail to undergo karyokinesis and/or cytokinesis and therefore become polyploid or binucleated, a key process in terminal CM differentiation. This switch from a diploid proliferative CM to a terminally differentiated polyploid CM remains an enigma and seems an obstacle for heart regeneration. Here, we set out to identify the transcriptional landscape of CMs around birth using single cell RNA sequencing (scRNA-seq) to predict transcription factors (TFs) involved in CM proliferation and terminal differentiation. To this end, we established an approa...
Source: Basic Research in Cardiology - March 2, 2023 Category: Cardiology Source Type: research
Single-cell RNA sequencing to identify cellular heterogeneity and targets in cardiovascular diseases: from bench to bedside
AbstractThe mechanisms of cardiovascular diseases (CVDs) remain incompletely elucidated. Single-cell RNA sequencing (scRNA-seq) has enabled the profiling of single-cell transcriptomes at unprecedented resolution and throughput, which is critical for deciphering cardiovascular cellular heterogeneity and underlying disease mechanisms, thereby facilitating the development of therapeutic strategies. In this review, we summarize cellular heterogeneity in cardiovascular homeostasis and diseases as well as the discovery of potential disease targets based on scRNA-seq, and yield new insights into the promise of scRNA-seq technolog...
Source: Basic Research in Cardiology - February 7, 2023 Category: Cardiology Source Type: research
