Vascular Wall Endothelial Cells Research Articles

Advances in Glycolysis Metabolism of Atherosclerosis.

Glycolysis is an important way for various cells such as vascular wall endothelial cells, smooth muscle cells, macrophages, and other cells to obtain energy. In pathological conditions, it can participate in the process of AS by regulating lipid deposition, calcification, angiogenesis in plaques, etc., together with its metabolite lactic acid. Recent studies have shown that lactate-related lactylation modifications are ubiquitous in the human proteome and are involved in the regulation of various inflammatory diseases. Combined with the distribution and metabolic characteristics of cells in the plaque in the process of AS, glycolysis-lactate-lactylation modification may be a new entry point for targeted intervention in atherosclerosis in the future. Therefore, this article intends to elaborate on the role and mechanism of glycolysis-lactate-lactylation modification in AS, as well as the opportunities and challenges in targeted therapy, hoping to bring some help to relevant scholars in this field. In atherosclerosis, glycolysis, lactate, and lactylation modification as a metabolic sequence affect the functions of macrophages, smooth muscle cells, endothelial cells, lymphocytes, and other cells and interfere with processes such as vascular calcification and intraplaque neovascularization to influence the progression of atherosclerosis.

Angioedema and Shear Stress Modulate Endothelial Permeability Through gC1qR

Angioedema is characterized by swelling in the dermis, oropharyngolaryngeal tissue and/or gastrointestinal wall. In angioedema (AE), vascular wall permeability increases, which is largely due to the overproduction of bradykinin, an inflammatory mediator and vasodilator. The receptor for C1q, gC1qR, has also been identified to play important roles in many physiological/pathological responses. High molecular weight kininogen (HK) can bind to gC1qR on the surface of vascular wall endothelial cells, resulting in the assembly and activation of the kinin/kallikrein system, culminating in bradykinin production. Endothelial cells are sensitive to blood flow‐induced shear stress. It has been established that low shear stress can lead to endothelial cell inflammation and gC1qR upregulation. The goals of the present study are: 1) to investigate how bradykinin and angioedema patients' plasma impair vascular endothelial cell permeability under various shear stress conditions (physiological and pathological); and 2) to determine if a monoclonal antibody (mAb) 74.5.2 known to block the gC1qR/HK interaction can also effectively block this response. To this end, human umbilical vein endothelial cells (HUVECs) were grown to confluence in polycarbonate transwell plates and exposed to 30 minutes of shear stress (1, 5 and 10 dynes/cm2) in the presence or absence of bradykinin or angioedema patients' plasma. FITC‐conjugated bovine serum albumin (BSA) was added to the upper chamber of the transwells before shearing. Endothelial cell permeability was measured by the amount of FITC‐BSA leaked to the bottom chamber of the transwell at the end of the experiment. Cell surface gC1qR expression was measured using a solid‐phase ELISA. Endothelial cell morphology following treatment (shear stress, bradykinin and AE plasma) was quantified using immunofluorescence microscopy. To confirm that mAb 74.5.2 can effectively block HK binding to gC1qR, purified gC1qR was coated on a 96‐well microtiter plate. After incubation with 74.5.2, HK binding was measured using ELISA. The results demonstrated that both bradykinin and AE plasma can significantly enhance gC1qR expression and damage endothelial cell integrity (i.e. permeability), especially under low shear stress (1 dynes/cm2). Monoclonal antibody 74.5.2 could significantly inhibit HK binding to immobilized gC1qR (by more than 40%). These results suggest that gC1qR is a major mediator in angioedema, especially under pathological low shear stress. Inhibiting HK binding to gC1qR using 74.5.2 could be an effective therapeutic solution to prevent angioedema.Support or Funding InformationResearch funded by Berhane Ghebrehiwet through NIH Grant: 1 R56 AI122376‐01A1This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Influence of Short-Term Occlusion on Dynamics of Arterial Circulation in Calf Muscles

Research background and hypothesis. KAATSU training is a method based on workout in a local hypoxic environment. For the justifi cation of its a detailed vascular response to circulatory disturbances is required.Research aim. The aim of this study was to investigate the peculiarities of reactive hyperaemia depending on the duration of occlusion and preliminary fi lling with blood of the occluded limb.Research methods. Arterial blood-fl ow intensity was measured by vein-occlusion plethysmography after 1, 2, and 3 minutes of occlusions. When the occlusion cuff was quickly infl ated with air above 250 mmHg, the amount of blood in vessels was close to the conditions of physiological norm. While the leg was lifted above the heart level for 30 seconds, the amount of blood in the calf decreased. A slow blowing the air into the cuff created a situation when the amount of blood in vessels had increased before the blood-fl ow was arrested. Research results. The peak blood-fl ow in the reactive hyperaemia phase depends on the duration of the occlusion and on the degree of fi lling with blood of segment under occlusion. The peak blood-fl ow readings were registered after occlusions conducted when the amount of blood in the limb had decreased before the occlusion and the lowest blood-fl ow readings was registered after occlusion done with the increased fi lling of vessels. Discussion and conclusions. The initial fi lling of vessels with blood or the degree of tension of endothelial cells of vascular wall is the most signifi cant infl uence on blood fl ow activation after short-term occlusions.Keywords: blood flow arrest, reactive hyperaemia, occlusion plethysmography.

Drug carrier interaction with blood: a critical aspect for high-efficient vascular-targeted drug delivery systems.

Vascular wall endothelial cells control several physiological processes and are implicated in many diseases, making them an attractive candidate for drug targeting. Vascular-targeted drug carriers (VTCs) offer potential for reduced side effects and improved therapeutic efficacy, however, only limited therapeutic success has been achieved to date. This is perhaps due to complex interactions of VTCs with blood components, which dictate VTC transport and adhesion to endothelial cells. This review focuses on VTC interaction with blood as well as novel 'bio-inspired' designs to mimic and exploit features of blood in VTC development. Advanced approaches for enhancing VTCs are discussed along with applications in regenerative medicine, an area of massive potential growth and expansion of VTC utility in the near future.

Progression in metastasis of colorectal carcinoma

Globally, the incidence of colorectal carcinoma (CRC) ranks the third among all cancers. The incidence of CRC is continually increasing in China. Invasion and metastasis are the major causes of death. Metastasis is a complex multistep malignant process, including the detachment of tumor cells from the primary site, interaction of tumor cells with the surrounding extracellular matrix, entering into the circulation or lymph system, adhesion to the endothelial cells of vascular wall, migration of tumor cells into secondary sites, angiogenesis and formation of new metastases. This article reviews the recent research progress in aspects of the metastasis related genes, microRNAs, epithelial mesenchymal transition, tumor stem cells, and micro environment of colorectal cancer.

Fluid Flow Mechanotransduction in Vascular Smooth Muscle Cells and Fibroblasts

Understanding how vascular wall endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) sense and transduce the stimuli of hemodynamic forces (shear stress, cyclic strain, and hydrostatic pressure) into intracellular biochemical signals is critical to prevent vascular disease development and progression. ECs lining the vessel lumen directly sense alterations in blood flow shear stress and then communicate with medial SMCs and adventitial FBs to regulate vessel function and disease. Shear stress mechanotransduction in ECs has been extensively studied and reviewed. In the case of endothelial damage, blood flow shear stress may directly act on the superficial layer of SMCs and transmural interstitial flow may be elevated on medial SMCs and adventitial FBs. Therefore, it is also important to investigate direct shear effects on vascular SMCs as well as FBs. The work published in the last two decades has shown that shear stress and interstitial flow have significant influences on vascular SMCs and FBs. This review summarizes work that considered direct shear effects on SMCs and FBs and provides the first comprehensive overview of the underlying mechanisms that modulate SMC secretion, alignment, contraction, proliferation, apoptosis, differentiation, and migration in response to 2-dimensional (2D) laminar, pulsatile, and oscillating flow shear stresses and 3D interstitial flow. A mechanistic model of flow sensing by SMCs is also provided to elucidate possible mechanotransduction pathways through surface glycocalyx, integrins, membrane receptors, ion channels, and primary cilia. Understanding flow-mediated mechanotransduction in SMCs and FBs and the interplay with ECs should be helpful in exploring strategies to prevent flow-initiated atherosclerosis and neointima formation and has implications in vascular tissue engineering.

Hybrid Adipogenic Implants from Adipose Stem Cells for Soft Tissue Reconstruction In Vivo

A critical barrier in tissue regeneration is scale-up. Bioengineered adipose tissue implants have been limited to ∼10 mm in diameter. Here, we devised a 40-mm hybrid implant with a cellular layer encapsulating an acellular core. Human adipose-derived stem cells (ASCs) were seeded in alginate. Poly(ethylene)glycol-diacrylate (PEGDA) was photopolymerized into 40-mm-diameter dome-shaped gel. Alginate-ASC suspension was painted onto PEGDA surface. Cultivation of hybrid constructs ex vivo in adipogenic medium for 28 days showed no delamination. Upon 4-week in vivo implantation in athymic rats, hybrid implants well integrated with host subcutaneous tissue and could only be surgically separated. Vascularized adipose tissue regenerated in the thin, painted alginate layer only if ASC-derived adipogenic cells were delivered. Contrastingly, abundant fibrous tissue filled ASC-free alginate layer encapsulating the acellular PEGDA core in control implants. Human-specific peroxisome proliferator-activated receptor-γ (PPAR-γ) was detected in human ASC-seeded implants. Interestingly, rat-specific PPAR-γ was absent in either human ASC-seeded or ASC-free implants. Glycerol content in ASC-delivered implants was significantly greater than that in ASC-free implants. Remarkably, rat-specific platelet/endothelial cell adhesion molecule (PECAM) was detected in both ASC-seeded and ASC-free implants, suggesting anastomosis of vasculature in bioengineered tissue with host blood vessels. Human nuclear staining revealed that a substantial number of adipocytes were of human origin, whereas endothelial cells of vascular wall were of chemaric human and nonhuman (rat host) origins. Together, hybrid implant appears to be a viable scale-up approach with volumetric retention attributable primarily to the acellular biomaterial core, and yet has a biologically viable cellular interface with the host. The present 40-mm soft tissue implant may serve as a biomaterial tissue expander for reconstruction of lumpectomy defects.

Computational model for adaptive fiber‐strengthened endothelial cell layers under flow induced shear‐stress

AbstractEndothelial cells, covering the inner surface of human vessels and the heart are permanently exposed to fluid shear stress which strongly affects endothelial structure and function. Due to their location at the interface between blood‐flow and the vascular wall endothelial cells play an essential role in hemodynamics. We present a complex computational model based on the Navier‐Stokes equations, Donell's shell equations, and additional constitutive systems of equations for the description of the flow around and inside of endothelial cells. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

The Intrinsic Coagulation/Kinin-Forming Cascade: Assembly in Plasma and Cell Surfaces in Inflammation

Publisher Summary This chapter discusses the intrinsic coagulation/kinin-forming cascade. The plasma kinin-forming system consists of three essential plasma proteins that interact upon binding to certain negatively charged surfaces or macromolecular complexes. These are coagulation factor XII (Hageman factor or HF), prekallikrein, and high-molecular-weight kininogen (HK). The rate of factor XII conversion to factor XIIa is dependent on each protein of the kinin-forming pathway, and thus all the proteins are coagulation factors. This intrinsic coagulation/kinin-forming cascade is in equilibrium in plasma even in the absence of any exogenous surface—that is, there is a finite rate at which activation occurs continuously, but plasma inhibitors hold the system in check. The addition of a macromolecular surface augments the activation rate such that the significant generation of bradykinin occurs; then a combination of kininases and protease inhibitors re-establish the equilibrium. Certain blood cells and vascular wall endothelial cells are capable of binding the proteins of the kinin-forming cascade. Thus, activation may preferentially occur along the cell surface and some of the binding proteins may actually function as endogenous activators.