Are telocytes related to maintenance of vascular homeostasis in normal and pathological aorta?

The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm or acute dissection (TAAD).

LIPCAR levels in plasma-derived extracellular vesicles is associated with left ventricle remodeling post-myocardial infarction.

Background: Long Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known.

Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression.

Aims: IgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.

The thromboxane receptor antagonist promotes beneficial adaptation and preserves cardiac function in experimental models of right heart overload.

Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure leading to right ventricular (RV) failure. While current PAH therapies improve patient outlook, they show limited benefit in attenuating RV dysfunction. Recent investigations demonstrated that the thromboxane (TX) A receptor (TP) antagonist attenuates experimental PAH across key hemodynamic parameters in the lungs and heart.

DHA, RvD1, RvD5, and MaR1 reduce human coronary arteries contractions induced by PGE.

In patients with coronary artery disease (CAD), plasma levels of pro-inflammatory lipid mediators such as PGE and TxA are increased. They could increase vascular contraction while EPA and DHA could reduce it. Studies have been mostly conducted on animal vessels.

Smooth Muscle Cell Relaxation Worsens Aortic Dilatation and Clinical Presentation in a BAPN/Angiotensin II-Induced Aortic Dissection Model in Rats.

Introduction: Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats.

Conductance Artery Wall Layers and Their Respective Roles in the Clearance Functions.

Evolutionary organization of the arterial wall into layers occurred concomitantly with the emergence of a highly muscularized, pressurized arterial system that facilitates outward hydraulic conductance and mass transport of soluble substances across the arterial wall. Although colliding circulating cells disperse potential energy within the arterial wall, the different layers counteract this effect: (1) the endothelium ensures a partial barrier function; (2) the media comprises smooth muscle cells capable of endocytosis/phagocytosis; (3) the outer adventitia and perivascular adipocytic tissue are the final receptacles of convected substances. While the endothelium forms a physical and a biochemical barrier, the medial layer is avascular, relying on the specific permeability properties of the endothelium for metabolic support.

Lim Domain Binding 3 (Ldb3) Identified as a Potential Marker of Cardiac Extracellular Vesicles.

Extracellular vesicles (EVs) are considered as transporters of biomarkers for the diagnosis of cardiac diseases, playing an important role in cell-to-cell communication during physiological and pathological processes. However, specific markers for the isolation and analysis of cardiac EVs are missing, imposing limitation on understanding their function in heart tissue. For this, we performed multiple proteomic approaches to compare EVs isolated from neonate rat cardiomyocytes and cardiac fibroblasts by ultracentrifugation, as well as EVs isolated from minced cardiac tissue and plasma by EVtrap.

Regulation and impact of cardiac lymphangiogenesis in pressure-overload-induced heart failure.

Aims: Lymphatics are essential for cardiac health, and insufficient lymphatic expansion (lymphangiogenesis) contributes to development of heart failure (HF) after myocardial infarction. However, the regulation and impact of lymphangiogenesis in non-ischaemic cardiomyopathy following pressure-overload remains to be determined. Here, we investigated cardiac lymphangiogenesis following transversal aortic constriction (TAC) in C57Bl/6 and Balb/c mice, and in end-stage HF patients.

The resolvin D2 - GPR18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice.

Chronic inflammation in atherosclerosis reflects a failure in the resolution of inflammation. Pro-resolving lipid mediators derived from omega-3 fatty acids reduce the development of atherosclerosis in murine models. The aim of the present study was to decipher the role of the specialized proresolving mediator (SPM) resolvin D2 (RvD2) in atherosclerosis and its signaling through the G-protein coupled receptor (GPR) 18.

Neuroimmune cardiovascular interfaces control atherosclerosis.

Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes. As plaques lack innervation, the effects of neuronal control on atherosclerosis remain unclear. However, the immune system responds to plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia).

Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm.

Pathological vascular remodeling is the underlying cause of atherosclerosis and abdominal aortic aneurysm (AAA). Here, we analyzed the role of galectin-1 (Gal-1), a β-galactoside-binding protein, as a therapeutic target for atherosclerosis and AAA. Mice lacking Gal-1 () developed severe atherosclerosis induced by pAAV/D377Y-mPCSK9 adenovirus and displayed higher lipid levels and lower expression of contractile markers of vascular smooth muscle cells (VSMCs) in plaques than wild-type mice.

From organic and inorganic phosphates to valvular and vascular calcifications.

Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, ageing, diabetes, and chronic kidney disease. This review aims to better understand how extracellular phosphates and their ability to be retained as calcium phosphates on the extracellular matrix initiate the mineralization process of arteries and valves. In this context, the physiological process of bone mineralization remains a human model for pathological soft tissue mineralization.

The VWF/LRP4/αVβ3-axis represents a novel pathway regulating proliferation of human vascular smooth muscle cells.

Aims: Von Willebrand factor (VWF) is a plasma glycoprotein involved in primary haemostasis, while also having additional roles beyond haemostasis namely in cancer, inflammation, angiogenesis, and potentially in vascular smooth muscle cell (VSMC) proliferation. Here, we addressed how VWF modulates VSMC proliferation and investigated the underlying molecular pathways and the in vivo pathophysiological relevance.

Methods And Results: VWF induced proliferation of human aortic VSMCs and also promoted VSMC migration.

Regulation of SMC traction forces in human aortic thoracic aneurysms.

Smooth muscle cells (SMCs) usually express a contractile phenotype in the healthy aorta. However, aortic SMCs have the ability to undergo profound changes in phenotype in response to changes in their extracellular environment, as occurs in ascending thoracic aortic aneurysms (ATAA). Accordingly, there is a pressing need to quantify the mechanobiological effects of these changes at single cell level.

CD31 Mimetic Coating Enhances Flow Diverting Stent Integration into the Arterial Wall Promoting Aneurysm Healing.

Background And Purpose: Beyond aneurysmal occlusion, metallic flow diverters (FDs) can induce an adverse endovascular reaction due to the foreignness of metal devices, hampering FD endothelialization across the aneurysm neck, and arterial healing of intracranial aneurysms. Here, we evaluated the potential benefits of an FD coating mimicking CD31, a coreceptor critically involved in endothelial function and endovascular homeostasis, on the endothelialization of FDs implanted in vivo.

Methods: Nitinol FD (Silk Vista Baby) and flat disks were dip-coated with a CD31-mimetic peptide via an intermediate layer of polydopamine.

Oral microbiota and atherothrombotic carotid plaque vulnerability in periodontitis patients. A cross-sectional study.

Background: An increased risk of atherothrombotic vascular events has been reported in periodontitis patients. Periodontitis is associated with dysbiotic subgingival biofilms and bacteremia.

Objective: We hypothesized (a) that the oral microbiome is associated with the carotid microbiome and (b) that periodontitis could contribute to plaque vulnerability.

[William Harvey reinterpreted in the light of species evolution (II) - Physiological and pathological consequences of the evolution of circulation].

In the first part of this review [22], "How and why circulatory phylogenesis fits into the evolution of species", we explained that the acquisition of a high-pressure arterial sector, as originally described by William Harvey in 1619, was the consequence, during evolution, of the appearance of vasomotor tone, inducing systemic friction forces (peripheral resistances), which, regulated locally (by vasodilatation), allows to adapt metabolic needs to the demand of functionally active territories. In this second part, we will try to understand how this phylogenesis directly influences the physiology, then the pathologies of the circulatory system in humans which are largely predominant, but not exclusively.

[William Harvey reinterpreted in the light of species evolution (I) - How and why circulation phylogenesis integrates itself within species evolution].

In this first part we describe the different steps of the evolution of species and the circulatory modifications, which accompany it. From the open circulation in invertebrates, via the in-series closed circulation in fish, to the in-parallel closed circulation in mammals, the local ability to vasodilate in relation to the specific metabolic demand of territorial activity was the driving force for circulatory evolution. This capacity was achieved by the progressive muscularization of small arteries, generating frictional forces, which systemically determine high arterial pressure, and locally determine active vasodilation via the inhibition of vasomotor tone.

Preclinical validation of therapeutic targets predicted by tensor factorization on heterogeneous graphs.

Incorrect drug target identification is a major obstacle in drug discovery. Only 15% of drugs advance from Phase II to approval, with ineffective targets accounting for over 50% of these failures. Advances in data fusion and computational modeling have independently progressed towards addressing this issue.

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases.

As the main particulate component of the circulating blood, RBCs play major roles in physiological hemodynamics and impact all arterial wall pathologies. RBCs are the main determinant of blood viscosity, defining the frictional forces exerted by the blood on the arterial wall. This function is used in phylogeny and ontogeny of the cardiovascular (CV) system, allowing the acquisition of vasomotricity adapted to local metabolic demands, and systemic arterial pressure after birth.

Selective inhibition of carboxypeptidase U may reduce microvascular thrombosis in rat experimental stroke.

Background: Carboxypeptidase U (CPU, CPB2, TAFIa) is a potent attenuator of fibrinolysis. The inhibition of CPU is thus an interesting strategy for improving thrombolysis.

Objectives: The time course of CPU generation and proCPU consumption were assessed in an experimental rat model of acute ischemic stroke (AIS).

Pathogenic variants in THSD4, encoding the ADAMTS-like 6 protein, predispose to inherited thoracic aortic aneurysm.

Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD.

Methods: We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients.