Impact of Perivascular Adipose Tissue on Neointimal Formation Following Endovascular Placement.

Following the placement of endovascular implants, perivascular adipose tissue (PVAT) becomes an early sensor of vascular injury to which it responds by undergoing phenotypic changes characterized by reduction in the secretion of adipocyte-derived relaxing factors and a shift to a proinflammatory and pro-contractile state. Thus, activated PVAT loses its anti-inflammatory function, secretes proinflammatory cytokines and chemokines, and generates reactive oxygen species, which are accompanied by differentiation of fibroblasts into myofibroblasts and proliferation of smooth muscle cells. These subsequently migrate into the intima, leading to intimal growth.

Targeting Rho kinase to restore endothelial barrier function following vascular scaffold implantation.

Vascular scaffold implantation induces injury to the intimal layer and causes discontinuity of the regenerated endothelial monolayer, compromising barrier integrity, increasing permeability, and allowing the transmigration of leukocytes and lipoproteins into the subendothelial space. Mechanical vascular wall stretching triggers Ras homolog family member A (RhoA)/Rho kinase-mediated actomyosin contractility and destabilization of adherens junctions, leading to endothelial barrier dysfunction. Assembly of intercellular adhesion and actin cytoskeletal organization of interendothelial junctions are controlled by downregulation of RhoA guanosine triphosphatase (GTPase)-mediated barrier-disruptive activity and upregulation of repressor-activator protein 1 (Rap1) and Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-mediated cytoskeletal reorganization, leading to endothelial barrier stabilization.

Optimization of preparation parameters of ceramic pot water filters for potential application of microbial and fluoride removal from groundwater.

The need to make clean water accessible and affordable for low-income countries is crucial. This study examines the suitability of various clays for Ceramic Pot Water Filters production and groundwater treatment for effective microbe and fluoride removal. For this study, three clays were collected from different geographical locations in Ethiopia,i.

Targeting glycoprotein VI to disrupt platelet-mediated tumor cell extravasation.

Activated platelets coat circulating tumor cells, protecting them from shear stress in the blood stream and promoting their evasion from immune surveillance. Platelets promote tumor cell dissemination to distant organs by releasing transforming growth factor-β1 (TGF-β1) into the tumor microenvironment, which induces phenotypic changes to the epithelial-mesenchymal transition. This process facilitates tumor cell transendothelial extravasation and formation of early metastatic niches.

Investigation of Self-Healing Mortars with and without Bagasse Ash at Pre- and Post-Crack Times.

Cracks in typical mortar constructions enhance water permeability and degrade ions into the structure, resulting in decreased mortar durability and strength. In this study, mortar samples are created that self-healed their cracks by precipitating calcium carbonate into them. bacterium (10, 10 cells/mL), calcium lactate, fine aggregate, OPC-cement, water, and bagasse ash were used to make self-healing mortar samples.

Vasculature-on-chip for Assessment of Bioresorbable Scaffolds and Endothelial Barrier Integrity.

Endothelial cells adhere to one another through junctional structures formed by intercellular adhesion molecules. These intercellular proteins regulate barrier function in response to the hemodynamic shear rate and enable the selective passage of solutes and fluids across the endothelium. After endovascular device implantation, the endothelial barrier is compromised and becomes discontinuous, which increases permeability, allowing transmigration of leukocytes and lipoproteins and leading to the accumulation of lipid-laden foamy macrophages in the subendothelial space.

Investigation on Control Burned of Bagasse Ash on the Properties of Bagasse Ash-Blended Mortars.

In recent years, partial replacement of cement with bagasse ash has been given attention for construction application due to its pozzolanic characteristics. Sugarcane bagasse ash and fine bagasse particles are abundant byproducts of the sugar industries and are disposed of in landfills. Our study presents the effect of burning bagasse at different temperatures (300 °C and 600 °C) on the compressive strength and physical properties of bagasse ash-blended mortars.

Impact of Reticulated Platelets on Platelet Reactivity in Neonates.

Neonatal megakaryopoiesis and platelet turnover form a developmentally unique pattern by generating a pool of newly released reticulated platelets from the bone marrow into the circulation. Reticulated platelets are more reactive and hyperaggregable compared to mature platelets, due to their high residual mRNA content, large size, increased expression of platelet surface receptors, and degranulation. The proportion of reticulated platelets in neonates is higher compared to that in adults.

Targeting heme-oxidized soluble guanylate cyclase to promote osteoblast function.

The enzyme soluble guanylate cyclase (sGC) plays an essential part in the nitric oxide (NO) signaling pathway by binding to the prosthetic heme group; thereby catalyzing the synthesis of cyclic guanosine monophosphate (cGMP)-dependent protein kinases. Impaired NO-sGC-cGMP signaling could lead to osteoblast apoptosis by mechanisms involving the oxidative-stress-induced shift of the redox state of the reduced heme to oxidized sGC, leading to diminished heme binding to the enzyme and rendering the sGC unresponsive to NO. Targeting oxidized sGC to enhance cGMP production could restore proliferation and differentiation of osteoblasts into osteocytes.

Involvement of Vitamin K-Dependent Proteins in Vascular Calcification.

Vascular calcification results from an imbalance of promoters and inhibitors of mineralization in the vascular wall, culminating in the creation of an organized extracellular matrix deposition. It is characterized by the accumulation of calcium phosphate complex and crystallization of hydroxyapatite in the tunica media, leading to vessel stiffening. The underlying initiators of dysregulated calcification maintenance are diverse.

Bioresorbable Scaffold-Based Controlled Drug Delivery for Restenosis.

Bioresorbable scaffolds have emerged as a potential alternative to non-erodible metal implants to alleviate the long-term risk of permanent device vascular implant-related adverse events. Bioresorbable scaffolds provide a temporary mechanical support function until the vessel reaches complete healing, and the implant progressively disappears and vasomotion resumes. A polymer matrix with embedded drugs coated onto the scaffold surface degrades slowly, reducing the size from the exterior toward the interior, and this allows controlled drug release to a local vascular segment.

Periadventitial local drug delivery to target restenosis.

The adventitia functions as a dynamic compartment for cell trafficking into and out of the artery wall, and communicates with medial and intimal cells. The resident cells in the tunica adventitia play an integral role in the regulation of vessel wall structure, repair, tone, and remodeling. Following injury to the vascular wall, adventitial fibroblasts are activated, which proliferate and differentiate into migratory myofibroblasts, and initiate inflammation through the secretion of soluble factors such as chemokines, cytokines, and adhesion molecules.

Distinct characteristics of neonatal platelet reactivity.

Platelets undergo a process of developmental maturation, and hence its regulation of vascular integrity and control of hemostasis at various stages of neonatal ages deserves better characterization. Functional assays for platelets require a larger volume of blood than what is feasible to collect in neonates, creating a technical hurdle that has been a challenge to investigate neonatal platelets. For this reason, the current knowledge of neonatal platelet function has been based on studies from cord blood-derived platelets as a surrogate for neonatal peripheral blood.

Local arterial wall drug delivery using balloon catheter system.

Balloon-based drug delivery systems allow localized application of drugs to a vascular segment to reduce neointimal hyperplasia and restenosis. Drugs are coated onto balloons using excipients as drug carriers to facilitate adherence and release of drug during balloon inflation. Drug-coated balloon delivery system is characterized by a rapid drug transfer that achieves high drug concentration along the vessel wall surface, intended to correspond to the balloon dilation-induced vascular injury and healing processes.

Bioresorbable vascular scaffolds: Biodegradation, drug delivery and vascular remodeling.

The metallic stents with durable polymers have been effective in reducing the need for revascularization, but the permanent presence of the metal and polymer have been associated with persistent inflammation, hypersensitivity reactions and incidence of thrombosis. Recent innovations of bioresorbable polymers are in development which could serve as temporary scaffolds that degrade into molecules and eventually resorb overtime, and leave the artery free of any permanent prosthetic constraints. The transient scaffolding has the advantages of restoring blood vessel to natural state, improve vasomotor tone and increase lumen enlargement because of expansive remodeling following completion of polymer resorption.

Endothelial Repair and Regeneration Following Intimal Injury.

Coronary artery intervention using device implants significantly reduce the risk of restenosis and the need for revascularization but are associated with endothelial denudation and impaired function. This may be due to incomplete endothelial recovery as a result of intimal injury, presence of polymer and/or high antiproliferative drug accumulation in the intima. The permanent presence of a metal prosthesis or polymer may impair the proliferation of resident endothelial cells to cover empty areas.

Involvement of platelets in tumor cell metastasis.

Extensive experimental evidence indicates that platelets contribute to tumor cell proliferation and metastasis through direct interactions and secreted bioactive proteins. Activated platelets release secretory factors that promote growth factors, chemokines, proangiogenic regulatory proteins, proteolytic enzymes and microparticles within the microenvironment to promote tumor cell growth and invasion. Furthermore, the formation of platelet-tumor cell heteroaggregates by integrin αIIbβ3 (glycoprotein IIb/IIIa) bridging plays an important role in tumor survival by forming a physical shield around tumor cells, and thereby protecting circulating tumor cells from immune-mediated lysis by natural killer (NK) cells.

Nonclinical aspects of venous thrombosis in pregnancy.

Pregnancy is a hypercoagulable state which carries an excess risk of maternal venous thrombosis. Endothelial injury, alterations in blood flow and activation of the coagulation pathway are proposed to contribute to the hypercoagulability. The risk for thrombosis may be accentuated by certain drugs and device implants that directly or indirectly affect the coagulation pathway.

Induction of nicotinamide-adenine dinucleotide phosphate oxidase and apoptosis by biodegradable polymers in macrophages: implications for stents.

The drug-eluting stent platform has a limited surface area, and a polymer carrier matrix is coated to enable sufficient loading of drugs. The development of a suitable polymer has been challenging because it must exhibit biocompatibility with the intravascular milieu. The use of biodegradable polymers seems to be attractive because it enables drug release as it degrades and is eventually eliminated from the body leaving the permanent metallic stent polymer-free.

Paclitaxel potentiates inflammatory cytokine-induced prothrombotic molecules in endothelial cells.

To overcome the limitations of balloon expandible metal stent-induced neointimal smooth muscle cell proliferation, drug-coated stent devices have been developed. Drug eluting stents release high concentrations of antiproliferative agents, such as paclitaxel, to reduce neointimal hyperplasia. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), is known to cause severe endothelial dysfunction and accelerate atherosclerotic lesion progression.

Platelet function in intravascular device implant-induced intimal injury.

Platelets are involved in the rapid response to intimal injury in which the underlying thrombogenic subendothelial matrix is exposed, leading to platelet adhesion, secretion, aggregation, and initiation of arterial thrombus formation. The platelet activation pathway involves a multistep process of distinct receptors, adhesive ligands, release of mediators, receptor-ligand interactions, and recruitment of more platelets to the site of injury. The balance between blood fluidity and intimal injury-induced arterial thrombosis is maintained by an intact endothelium that controls vessel tone, synthesizes inhibitors and activators of platelet function, and thereby allows the free flow of blood cell elements.

Drug release kinetics from stent device-based delivery systems.

In an effort to overcome the limitations of balloon-expandible intravascular metal stent-induced neointimal formation, drug-coated stent devices have been developed. The stent platform allows the local delivery of drugs to an injury site, thereby reducing the amount of drug exposure to the systemic circulation and other organs. The drug carrier matrix allows the release of the drug in a diffusion-controlled manner over an extended time period after the stent implant.

Endothelial injury in the initiation and progression of vascular disorders.

Endothelial cell dysfunction is considered to be an early event which subsequently leads to vascular wall disorders. Ultrastructural studies indicate that the endothelial cell changes involve membrane damage, increased permeability, swelling and necrosis. The endothelial cell loss of function could be as a result of changes in hemodynamic forces (shear and/or hoop stress), direct drug-induced cytotoxicity, mechanical device implant-induced injury and/or immune-mediated mechanisms.

Local vascular toxicokinetics of stent-based drug delivery.

One of the major limitations of balloon angioplasty is early restenosis as a result of elastic recoil leading to vessel occlusion. The constrictive (negative) remodeling of the blood vessel is overcome by implanting a balloon expandible metal stent to dilate the artery and thereby prevent elastic recoil. However, bare metal stent implants cause mechanical injury to the intima and release of inflammatory mediators which then initiates formation of neointimal layer leading to restenosis.

Inhibition of mammalian target of rapamycin modulates expression of adhesion molecules in endothelial cells.

Neointimal hyperplasia often follows angioplasty-induced arterial injury or stenting and results in restenosis. Previous reports have suggested that arterial injury activates complement which amplifies inflammatory responses that may initiate and sustain neointimal hyperplasia. The effects of rapamycin on complement-induced expression of intracellular adhesion molecules (ICAMs) were examined in porcine arterial endothelial cell (PAEC) line that was transformed with large T antigen.