Leukocytes use endothelial membrane tunnels to extravasate the vasculature.

Upon inflammation, leukocytes extravasate through endothelial cells. When they extravasate, it is generally accepted that neighboring endothelial cells disconnect. Careful examination of endothelial junctions showed a partial membrane overlap beyond VE-cadherin distribution.

Long Non-coding RNA Based Therapy for Cardiovascular Disease.

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, necessitating innovative therapeutic strategies. Long non-coding RNAs (lncRNAs) have emerged as regulators of gene expression, influencing various cellular processes involved in cardiovascular health and disease. This review explores the functional roles of lncRNAs in CVD pathogenesis, highlighting their involvement in processes such as hypertrophy, fibrosis, inflammation, and vascular remodeling.

Clonal haematopoiesis of indeterminate potential and mortality in coronary artery disease.

Background And Aims: Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with cardiovascular risk, but its prognostic relevance and mechanistic role in coronary artery disease (CAD) remains incompletely understood. This study investigated the association between CHIP and all-cause mortality in CAD and explored the cellular and molecular mechanisms, focusing on TET2 mutations.

Methods: Targeted deep sequencing of 13 CHIP driver genes in 8612 patients with angiographically confirmed CAD was performed.

Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure - interaction between loss of Y chromosome and clonal haematopoiesis.

Aims: Age-associated clonal haematopoiesis of indeterminate potential (CHIP) has been linked to increased incidence and worse prognosis of chronic heart failure (CHF). CHIP arises from somatic mutations in haematopoietic stem and progenitor cells. Mosaic loss of Y chromosome (LOY), the most common somatic mutation in male blood cells, increases with age, drives clonal expansion of myeloid cells, and has been experimentally associated with cardiac fibrosis and heart failure in mice.

Neural Mechanisms in Cardiovascular Health and Disease.

Although the neurocardiac axis is central to cardiovascular homeostasis, its dysregulation drives heart failure and cardiometabolic diseases. This review examines the bidirectional interplay between the autonomic nervous system and the heart, highlighting the role of this interplay in disease progression and its therapeutic potential. The autonomic nervous system modulates cardiac function and vascular tone through its sympathetic and parasympathetic branches.

A cell type-specific expression atlas of small and total RNA in the heart after myocardial infarction.

Acute myocardial infarction (AMI) is a leading cause of mortality worldwide. MicroRNAs (miRNAs), among other small non-coding RNAs, shape the transcriptome and control cellular functions. Although single-cell technologies are now available to study myocardial ischemia response, the study of small RNA regulation is limited by depth of expression, capture efficiency and lack of full coverage of transcripts.

Targeting miRNA-1a and miRNA-15b: A Novel Combinatorial Strategy to Drive Adult Cardiac Regeneration.

Despite its promise, cardiac regenerative therapy remains clinically elusive due to the difficulty of spatio-temporal control of proliferative induction, and the need to coordinately reprogram multiple regulatory pathways to overcome the strict post-mitotic state of human adult cardiomyocytes. To address this unmet therapeutic need, a combinatorial miRNA interference screen is performed specifically targeting cardiac-predominant miRNAs regulating key aspects of cardiomyocyte mitotic induction to cell-cycle completion in neonatal rat cardiomyocytes. In doing so combinatorial interference of miRNA-1a and miRNA-15b (LNA-1a/15b) is identified as drivers of adult cardiomyocyte proliferation.

Decoding subcellular RNA localization one molecule at a time.

Eukaryotic cells are highly structured and composed of multiple membrane-bound and membraneless organelles. Subcellular RNA localization is a critical regulator of RNA function, influencing various biological processes. At any given moment, RNAs must accurately navigate the three-dimensional subcellular environment to ensure proper localization and function, governed by numerous factors, including splicing, RNA stability, modifications, and localizing sequences.

Extracellular Matrix Proteins Improve Risk Prediction in Patients Undergoing Transcatheter Aortic Valve Replacement.

Background: Cardiac fibrosis is common in patients with severe aortic stenosis and an independent predictor of death. Therefore, we examined the additional value of circulating fibrosis markers as a putative biomarker platform to identify patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) who are at a higher risk of death.

Methods: In this study, 2-year survival analyses were conducted in 378 consecutive patients undergoing TAVR to evaluate the association between fibrosis marker and risk of adverse long-term outcome.

Roadmap for alleviating the manifestations of ageing in the cardiovascular system.

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing.

Mosaic loss of Y chromosome and mortality after coronary angiography.

Background And Aims: Acquired somatic mutations emerged as important drivers of adverse cardiovascular disease outcomes. Recently, mosaic loss of Y chromosome (LOY) in haematopoietic cells was identified to induce diffuse cardiac fibrosis in male mice. The aim of the present study was to determine the association between LOY and cardiovascular mortality in patients undergoing coronary angiography.

Temporal Expression Analysis to Unravel Gene Regulatory Dynamics by microRNAs.

MicroRNAs (miRNAs) are a class of small non-coding RNAs (sncRNAs) of length 21-25 nucleotides. These sncRNAs hybridize to repress their target genes and inhibit protein translation, thereby controlling regulatory functions in the cell. Integration of time-series matched small and RNA-seq data enables investigation of dynamic gene regulation through miRNAs during development or in response to a stimulus, such as stress.

Inhibition of miR-92a normalizes vascular gene expression and prevents diastolic dysfunction in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) remains a major public health burden with increasing prevalence but only few effective therapies. Endothelial dysfunction and inflammation are identified as pathophysiological drivers of HFpEF disease progression. MicroRNAs are increasingly recognized as key regulators of these pathological processes, while antimiR-based therapies have been emerged as promising therapeutics in mice and humans.

Site-specific m6A-miR-494-3p, not unmethylated miR-494-3p, compromises blood brain barrier by targeting tight junction protein 1 in intracranial atherosclerosis.

Background And Purpose: Intracranial atherosclerosis is one of the most common causes of ischaemic stroke. However, there is a substantial knowledge gap on the development of intracranial atherosclerosis. Intracranial arteries are characterized by an upregulation of tight junctions between endothelial cells, which control endothelial permeability.

Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease.

Background: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice.

Endothelial Heterogeneity in the Response to Autophagy Drives Small Vessel Muscularization in Pulmonary Hypertension.

Background: Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark of pulmonary hypertension (PH). Yet, why some ECs die and others proliferate and how this contributes to vascular remodeling is unclear. We hypothesized that this differential response may: (1) relate to different EC subsets, namely pulmonary artery (PAECs) versus microvascular ECs (MVECs); (2) be attributable to autophagic activation in both EC subtypes; and (3) cause replacement of MVECs by PAECs with subsequent distal vessel muscularization.

Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

Aim: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials.

Methods And Results: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.

Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.

Design, Setting, And Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age.

Targeting cardiomyocyte cell cycle regulation in heart failure.

Heart failure continues to be a significant global health concern, causing substantial morbidity and mortality. The limited ability of the adult heart to regenerate has posed challenges in finding effective treatments for cardiac pathologies. While various medications and surgical interventions have been used to improve cardiac function, they are not able to address the extensive loss of functioning cardiomyocytes that occurs during cardiac injury.

[Heart and blood: clonal hematopoiesis].

Cardiovascular diseases are among the leading causes of death worldwide, with well-known modifiable risk factors, such as smoking, overweight, lipid metabolism disorders, lack of physical activity and high blood pressure playing a significant role. Recent studies have now identified "clonal hematopoiesis" as a novel blood-based risk factor. Clonal hematopoiesis arises from mutations in hematopoietic stem cells, which lead to the expansion of mutated blood cells.

Endothelial cells drive organ fibrosis in mice by inducing expression of the transcription factor SOX9.

Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it is unclear to what extent endothelial cells also might contribute. We detected increased expression of the transcription factor in endothelial cells in several different mouse fibrosis models.