A timeline study on vascular co-morbidity induced cerebral endothelial dysfunction assessed by perfusion MRI.

Endothelial dysfunction is considered a key element in the early pathogenesis of neurodegenerative disorders. Dysfunction of the cerebral endothelial cells can result in dysregulation of cerebral perfusion and disruption of the Blood Brain Barrier (BBB), leading to brain damage, neurodegeneration and cognitive decline. It has been shown that the presence of modifiable risk factors exacerbates endothelial dysfunction.

Smad1/5 is acetylated in the dorsal aortae of the mouse embryo before the onset of blood flow, driving early arterial gene expression.

Aims: During embryonic development, arteriovenous (AV) differentiation ensures proper blood vessel formation and maturation. Defects in arterial or venous identity cause inappropriate fusion of vessels, resulting in atypical shunts, so-called AV malformations (AVMs). Currently, the mechanism behind AVM formation remains unclear, and treatment options are fairly limited.

Cell signaling and tissue remodeling in the pulmonary autograft after the Ross procedure: A computational study.

In the Ross procedure, a patient's pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale.

Origin and flow-mediated remodeling of the murine and human extraembryonic circulation systems.

The transduction of mechanical stimuli produced by blood flow is an important regulator of vascular development. The vitelline and umbilico-placental circulations are extraembryonic vascular systems that are required for proper embryonic development in mammalian embryos. The morphogenesis of the extraembryonic vasculature and the cardiovascular system of the embryo are hemodynamically and molecularly connected.

Intravoxel incoherent motion as a surrogate marker of perfused vascular density in rat brain.

Intravoxel incoherent motion (IVIM) MRI has emerged as a valuable technique for the assessment of tissue characteristics and perfusion. However, there is limited knowledge about the relationship between IVIM-derived measures and changes at the level of the vascular network. In this study, we investigated the potential use of IVIM MRI as a noninvasive tool for measuring changes in cerebral vascular density.

Pericyte loss initiates microvascular dysfunction in the development of diastolic dysfunction.

Aims: Microvascular dysfunction has been proposed to drive heart failure with preserved ejection fraction (HFpEF), but the initiating molecular and cellular events are largely unknown. Our objective was to determine when microvascular alterations in HFpEF begin, how they contribute to disease progression, and how pericyte dysfunction plays a role herein.

Methods And Results: Microvascular dysfunction, characterized by inflammatory activation, loss of junctional barrier function, and altered pericyte-endothelial crosstalk, was assessed with respect to the development of cardiac dysfunction, in the Zucker fatty and spontaneously hypertensive (ZSF1) obese rat model of HFpEF at three time points: 6, 14, and 21 weeks of age.

Mechanism of COVID-19-Induced Cardiac Damage from Patient, In Vitro and Animal Studies.

Purpose Of Review: Though patient studies have been important for understanding the disease, research done in animals and cell culture complement our knowledge from patient data and provide insight into the mechanism of the disease. Understanding how COVID causes damage to the heart is essential to understanding possible long-term consequences.

Recent Findings: COVID-19 is primarily a disease that attacks the lungs; however, it is known to have important consequences in many other tissues including the heart.

Q-VAT: Quantitative Vascular Analysis Tool.

As our imaging capability increase, so does our need for appropriate image quantification tools. Quantitative Vascular Analysis Tool (Q-VAT) is an open-source software, written for Fiji (ImageJ), that perform automated analysis and quantification on large two-dimensional images of whole tissue sections. Importantly, it allows separation of the vessel measurement based on diameter, allowing the macro- and microvasculature to be quantified separately.

Prevalence and Clinical Consequences of Multiple Pathogenic Variants in Dilated Cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) was considered a monogenetic disease that can be caused by over 60 genes. Evidence suggests that the combination of multiple pathogenic variants leads to greater disease severity and earlier onset. So far, not much is known about the prevalence and disease course of multiple pathogenic variants in patients with DCM.

Computational modeling reveals inflammation-driven dilatation of the pulmonary autograft in aortic position.

The pulmonary autograft in the Ross procedure, where the aortic valve is replaced by the patient's own pulmonary valve, is prone to failure due to dilatation. This is likely caused by tissue degradation and maladaptation, triggered by the higher experienced mechanical loads in aortic position. In order to further grasp the causes of dilatation, this study presents a model for tissue growth and remodeling of the pulmonary autograft, using the homogenized constrained mixture theory and equations for immuno- and mechano-mediated mass turnover.

Evaluation of Microvascular Rarefaction in Vascular Cognitive Impairment and Heart Failure (CRUCIAL): Study Protocol for an Observational Study.

Introduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel-related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these comorbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity.

SARS-CoV-2 infection causes prolonged cardiomyocyte swelling and inhibition of HIF1α translocation in an animal model COVID-19.

Recovered COVID-19 patients often display cardiac dysfunction, even after a mild infection. Most current histological results come from patients that are hospitalized and therefore represent more severe outcomes than most COVID-19 patients face. To overcome this limitation, we investigated the cardiac effects of SARS-CoV-2 infection in a hamster model.

Immunometabolic Mechanisms of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence worldwide, already accounting for at least half of all heart failure (HF). As most patients with HFpEF are obese with metabolic syndrome, metabolic stress has been implicated in syndrome pathogenesis. Recently, compelling evidence for bidirectional crosstalk between metabolic stress and chronic inflammation has emerged, and alterations in systemic and cardiac immune responses are held to participate in HFpEF pathophysiology.

AAV9-mediated functional screening for cardioprotective cytokines in Coxsackievirus-B3-induced myocarditis.

Viral myocarditis (VM) is an important cause of heart failure (HF) in children and adults. However, the molecular determinants involved in cardiac inflammation and cardiomyocyte necrosis remain poorly characterized, and cardioprotective molecules are currently missing. Here, we applied an in vivo method based on the functional selection (FunSel) of cardioprotective factors using AAV vectors for the unbiased identification of novel immunomodulatory molecules in a Coxsackievirus B3 (CVB3)-induced myocarditis mouse model.

Neutrophil inhibition improves acute inflammation in a murine model of viral myocarditis.

Aims: Viral myocarditis (VM) is an inflammatory pathology of the myocardium triggered by a viral infection that may cause sudden death or heart failure (HF), especially in the younger population. Current treatments only stabilize and improve cardiac function without resolving the underlying inflammatory cause. The factors that induce VM to progress to HF are still uncertain, but neutrophils have been increasingly associated with the negative evolution of cardiac pathologies.

Understanding Pulmonary Autograft Remodeling After the Ross Procedure: Stick to the Facts.

The Ross, or pulmonary autograft, procedure presents a fascinating mechanobiological scenario. Due to the common embryological origin of the aortic and pulmonary root, the conotruncus, several authors have hypothesized that a pulmonary autograft has the innate potential to remodel into an aortic phenotype once exposed to systemic conditions. Most of our understanding of pulmonary autograft mechanobiology stems from the remodeling observed in the arterial wall, rather than the valve, simply because there have been many opportunities to study the walls of dilated autografts explanted at reoperation.

Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity.

Endothelial cells throughout the body are heterogeneous, and this is tightly linked to the specific functions of organs and tissues. Heterogeneity is already determined from development onwards and ranges from arterial/venous specification to microvascular fate determination in organ-specific differentiation. Acknowledging the different phenotypes of endothelial cells and the implications of this diversity is key for the development of more specialized tissue engineering and vascular repair approaches.

Stabilin-1 mediates beneficial monocyte recruitment and tolerogenic macrophage programming during CVB3-induced viral myocarditis.

Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury and dysfunction. Stabilin-1 is a scavenger receptor that regulates several aspects of the innate immunity. Whether stabilin-1 affects the inflammatory response during viral myocarditis (VM) is entirely unknown.

Back to the root: a large animal model of the Ross procedure.

The excellent clinical outcomes of the Ross procedure and previous histological studies suggest that the pulmonary autograft has the potential to offer young patients a permanent solution to aortic valve disease. We aim to study the early mechanobiological adaptation of the autograft. To this end, we have reviewed relevant existing animal models, including the canine models which enabled Donald N Ross to perform the first Ross procedure in a patient in 1967.

Non-Invasive Evaluation of Cerebral Microvasculature Using Pre-Clinical MRI: Principles, Advantages and Limitations.

Alterations to the cerebral microcirculation have been recognized to play a crucial role in the development of neurodegenerative disorders. However, the exact role of the microvascular alterations in the pathophysiological mechanisms often remains poorly understood. The early detection of changes in microcirculation and cerebral blood flow (CBF) can be used to get a better understanding of underlying disease mechanisms.

Prdm16 Supports Arterial Flow Recovery by Maintaining Endothelial Function.

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Vessel Enlargement in Development and Pathophysiology.

From developmental stages until adulthood, the circulatory system remodels in response to changes in blood flow in order to maintain vascular homeostasis. Remodeling processes can be driven by formation of vessels or angiogenesis, and by the restructuration of already existing vessels, such as vessel enlargement and regression. Notably, vessel enlargement can occur as fast as in few hours in response to changes in flow and pressure.

An Model to Study Endothelialization of Cardiac Graft Tissues Under Flow.

Pulmonary valve replacement is performed with excellent resultant hemodynamics in patients that have underlying congenital or acquired heart valve defects. Despite recent advancements in right ventricular outflow tract reconstruction, an increased risk of developing infective endocarditis remains, which has a more common occurrence for conduits of bovine jugular vein (BJV) origin compared with cryopreserved homografts. The reason for this is unclear although it is hypothesized to be associated with an aberrant phenotypic state of cells that reendothelialize the graft tissue postimplantation.

Linagliptin prevents left ventricular stiffening by reducing titin cleavage and hypophosphorylation.

The metabolic syndrome (MetS) is an escalating problem worldwide, causing left ventricular stiffening, an early characteristic of diastolic dysfunction for which no treatment exists. As diastolic dysfunction and stiffening in MetS patients are associated with increased circulating dipeptidyl peptidase-4 (DPP-4) levels, we investigated whether the clinically approved DPP-4 inhibitor linagliptin reduces left ventricular stiffness in MetS-induced cardiac disease. Sixteen-week-old obese ZSF1 rats, displaying the MetS and left ventricular stiffness, received linagliptin-supplemented or placebo diet for four weeks.