Multiple cell types including melanocytes contribute to elastogenesis in the developing murine aortic valve.

Elastic fibers are crucial for aortic valve (AoV) function and are generated and maintained by valvular interstitial cells (VICs). VICs exhibit diverse phenotypes, yet the specific subpopulation responsible for producing and regulating elastic fibers remains unclear. This gap in knowledge is significant, given that elastin (Eln) abnormalities lead to congenital AoV defects and initiate AoV diseases.

Computational Model for Early-Stage Aortic Valve Calcification Shows Hemodynamic Biomarkers.

Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes.

The Systemic Effect of Ischemia Training and Its Impact on Bone Marrow-Derived Monocytes.

Objective: Monocytes are innate immune cells that play a central role in inflammation, an essential component during neovascularization. Our recent publication demonstrated that ischemia training by 24 h unilateral occlusion of the femoral artery (FA) can modify bone marrow-derived monocytes (BM-Mono), allowing them to improve collateral remodeling in a mouse model of hindlimb ischemia. Here, we expand on our previous findings, investigating a potential systemic effect of ischemia training and how this training can impact BM-Mono.

Mechanical stretch leads to increased caveolin-1 content and mineralization potential in extracellular vesicles from vascular smooth muscle cells.

Background: Hypertension-induced mechanical stress on vascular smooth muscle cells (VSMCs) is a known risk factor for vascular remodeling, including vascular calcification. Caveolin-1 (Cav-1), an integral structural component of plasma membrane invaginations, is a mechanosensitive protein that is required for the formation of calcifying extracellular vesicles (EVs). However, the role of mechanics in Cav-1-induced EV formation from VSMCs has not been reported.

Effect of chronic kidney disease induced calcification on peripheral vascular perfusion using near-infrared spectroscopic imaging.

Low-cost techniques that can detect the presence of vascular calcification (VC) in chronic kidney disease (CKD) patients could improve clinical outcomes. In this study, we established a near-infrared spectroscopy-based imaging technique to determine changes in peripheral hemodynamics due to CKD-induced VC. Mice were fed a high-adenine diet with either normal or high levels of phosphate to induce CKD with and without VC, respectively.

Freeze casting to engineer gradient porosity in hydroxyapatite-boron nitride nanotube composite scaffold for improved compressive strength and osteogenic potential.

Graded porosity plays a crucial role in scaffolds for bone tissue engineering as it facilitates vital processes such as nutrient diffusion, cellular infiltration, and tissue integration. This paper explores the utilization of freeze casting (FC) as a technique to generate composite scaffolds comprising hydroxyapatite (HA) reinforced with 1D-boron nitride nanotubes (BNNTs) featuring graded porosity and improved compressive strength. Comparative studies were conducted using FC at room and sub-zero temperatures to assess the influence of temperature gradient and heat transfer rate on the production of gradient and aligned porosity in HA-BNNT composites.

Altered Caveolin-1 Dynamics Result in Divergent Mineralization Responses in Bone and Vascular Calcification.

Introduction: Though vascular smooth muscle cells adopt an osteogenic phenotype during pathological vascular calcification, clinical studies note an inverse correlation between bone mineral density and arterial mineral-also known as the calcification paradox. Both processes are mediated by extracellular vesicles (EVs) that sequester calcium and phosphate. Calcifying EV formation in the vasculature requires caveolin-1 (CAV1), a membrane scaffolding protein that resides in membrane invaginations (caveolae).

Temporal Progression of Aortic Valve Pathogenesis in a Mouse Model of Osteogenesis Imperfecta.

Organization of extracellular matrix (ECM) components, including collagens, proteoglycans, and elastin, is essential for maintaining the structure and function of heart valves throughout life. Mutations in ECM genes cause connective tissue disorders, including Osteogenesis Imperfecta (OI), and progressive debilitating heart valve dysfunction is common in these patients. Despite this, effective treatment options are limited to end-stage interventions.

Spatial-Temporal Oxygenation Mapping Using a Near-Infrared Optical Scanner: Towards Peripheral Vascular Imaging.

Near-infrared spectroscopy (NIRS)-based peripheral perfusion, or microcirculation, can be used to assess the severity of peripheral vascular dysfunction. A low-cost, portable non-contact near-infrared optical scanner (NIROS) was developed for spatio-temporal mapping of tissue oxygenation and perfusion in tissues. In vivo validation studies were carried out on control subjects (n = 3) to assess the ability of NIROS to measure real-time oxygenation changes in response to an occlusion paradigm on the dorsum of the hand.

Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) exhibit tremendously elevated risk for cardiovascular disease, particularly ischemic heart disease, due to premature vascular and cardiac aging and accelerated ectopic calcification. The presence of cardiovascular calcification associates with increased risk in patients with CKD. Disturbed mineral homeostasis and diverse comorbidities in these patients drive increased systemic cardiovascular calcification in different manifestations with diverse clinical consequences, like plaque instability, vessel stiffening, and aortic stenosis.

Epidermal growth factor receptor inhibition prevents vascular calcifying extracellular vesicle biogenesis.

Chronic kidney disease (CKD) increases the risk of cardiovascular disease, including vascular calcification, leading to higher mortality. The release of calcifying extracellular vesicles (EVs) by vascular smooth muscle cells (VSMCs) promotes ectopic mineralization of vessel walls. Caveolin-1 (CAV1), a structural protein in the plasma membrane, plays a major role in calcifying EV biogenesis in VSMCs.

Analysis of Extracellular Vesicle-Mediated Vascular Calcification Using In Vitro and In Vivo Models.

Cardiovascular disease is the leading cause of death in the world, and vascular calcification is the most significant predictor of cardiovascular events; however, there are currently no treatment or therapeutic options for vascular calcification. Calcification begins within specialized extracellular vesicles (EVs), which serve as nucleating foci by aggregating calcium and phosphate ions. This protocol describes methods for obtaining and assessing calcification in murine aortas and analyzing the associated extracted EVs.

Membrane Remodeling of Human-Engineered Cardiac Tissue by Chronic Electric Stimulation.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show immature features, but these are improved by integration into 3D cardiac constructs. In addition, it has been demonstrated that physical manipulations such as electrical stimulation (ES) are highly effective in improving the maturation of human-engineered cardiac tissue (hECT) derived from hiPSC-CMs. Here, we continuously applied an ES in capacitive coupling configuration, which is below the pacing threshold, to millimeter-sized hECTs for 1-2 weeks.

Flap Endonuclease 1 Endonucleolytically Processes RNA to Resolve R-Loops through DNA Base Excision Repair.

Flap endonuclease 1 (FEN1) is an essential enzyme that removes RNA primers and base lesions during DNA lagging strand maturation and long-patch base excision repair (BER). It plays a crucial role in maintaining genome stability and integrity. FEN1 is also implicated in RNA processing and biogenesis.

Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.

Aims: Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.

Methods And Results: An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification.

The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification.

Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes.

S2 Heart Sound Detects Aortic Valve Calcification Independent of Hemodynamic Changes in Mice.

Background: Calcific aortic valve disease (CAVD) is often undiagnosed in asymptomatic patients, especially in underserved populations. Although artificial intelligence has improved murmur detection in auscultation exams, murmur manifestation depends on hemodynamic factors that can be independent of aortic valve (AoV) calcium load and function. The aim of this study was to determine if the presence of AoV calcification directly influences the S2 heart sound.

Pigmentation Affects Elastic Fiber Patterning and Biomechanical Behavior of the Murine Aortic Valve.

The aortic valve (AoV) maintains unidirectional blood distribution from the left ventricle of the heart to the aorta for systemic circulation. The AoV leaflets rely on a precise extracellular matrix microarchitecture of collagen, elastin, and proteoglycans for appropriate biomechanical performance. We have previously demonstrated a relationship between the presence of pigment in the mouse AoV with elastic fiber patterning using multiphoton imaging.

Highly Selective PPARα (Peroxisome Proliferator-Activated Receptor α) Agonist Pemafibrate Inhibits Stent Inflammation and Restenosis Assessed by Multimodality Molecular-Microstructural Imaging.

BACKGROUND New pharmacological approaches are needed to prevent stent restenosis. This study tested the hypothesis that pemafibrate, a novel clinical selective PPARα (peroxisome proliferator-activated receptor α) agonist, suppresses coronary stent-induced arterial inflammation and neointimal hyperplasia. METHODS AND RESULTS Yorkshire pigs randomly received either oral pemafibrate (30 mg/day; n=6) or control vehicle (n=7) for 7 days, followed by coronary arterial implantation of 3.

A surface-based calibration approach to enable dynamic and accurate quantification of colorimetric assay systems.

Colorimetry is widely used in assay systems for its low-cost, ease-of-use, rapidity, moderate storage requirements and intuitively visible effects. However, the application is limited due to its relatively low sensitivity. Conventional colorimetric calibration methods often use a fixed incubation time that can limit the detection range, system robustness and sensitivity.