Cells Of Human Blood Vessels Research Articles

Sol–gel-derived hierarchically wrinkled mesoporous ceramics for enhancement of cell alignment

Hierarchical ceramic structures offer great potential for multitudinous industrial applications (e.g., cell alignment) due to their intrinsic hydrophilic and environmental resistance properties. However, to date, the fabrication of hierarchical ceramic structures requires specific equipment (e.g., high vacuum systems) and time-consuming processes; such requirements limit the practical utilization of hierarchical ceramics. In this study, we combined ceramic thin films produced from interfacial sol–gel reactions and surface wrinkling from elastomer cross-linking contraction; we conducted a dynamic interfacial release process to fabricate hierarchically wrinkled mesoporous ceramic surfaces on soft elastomers. The parameters of sol–gel reactions, including precursors, acid/base-catalysts, aging time, and temperature, were systematically controlled to demonstrate the feasibility of sol–gel reactions for fabrication of hierarchically mesoporous ceramic wrinkled surfaces (i.e., mesopores on a microsized wrinkled surface). Furthermore, the wrinkled surfaces demonstrated great enhancement of growth alignment of human blood vessel cells. Thus, we developed a simple (yet cost-effective), mold-free, large-area, and hierarchical ceramic wrinkle formation process; it can be used in many practical applications, such as cell culture, microfluidic chips, antiskidding surfaces, antiglare structures, and photoelectric devices.

EYE ON CHINA

China approves five genetically modified crops. China’s science awards further encourage innovation. Severe and prolonged air pollution affects productivity of workers. Negative population growth looms ahead for China. Genetically-enhanced human blood vessel cells. New bat-borne virus related to Ebola. China’s homegrown anti-cancer drug wins international recognition. Tariff changes aim to cut drug prices. New procurement scheme to reduce drug prices. China brings more new drugs to market with fast-track approval. Tougher supervision vowed over food and drugs. Project seeks uniformity in treatment of China’s number one killer. Great potential seen in AI-powered medical imaging. Updates from China’s life sciences industry.

PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation

Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.

Function or Expansion: How to Investigate Cells of Human Blood Vessels

Function or Expansion: How to Investigate Cells of Human Blood Vessels

Human brain endothelial barrier cells are distinctly less vulnerable to silver nanoparticles toxicity than human blood vessel cells: A cell-specific mechanism of the brain barrier?

The blood–brain barrier (BBB) constitutes a distinctive and tightly regulated interface between the brain and the peripheral circulation. The objective of studies was to compare responses of human endothelial cells representing the model of blood vessels – EA.hy926 and HUVEC cells and the model of the brain endothelial barrier – HBEC5i cells to silver nanoparticles (SNPs). A contact of SNPs with endothelial cells resulted in a formation of SNP agglomerates. Consequently, the SNPs uptake by endothelial cells affected cell viability and membrane integrity however observed responses were different. Brain endothelial barrier HBEC5i cells were much less vulnerable to SNPs toxicity comparing to EA.hy926 and HUVEC cells. It can be ascribed to the presence of specialized cellular components of the brain barrier, protecting HBEC5i cells against toxic SNPs. Fundamental understanding of SNPs inducing the BBB dysfunction may initiate engineering novel SNPs which are safe for the BBB and thereby safe for the brain.

ProMMP-1 PRODUCTION BY CULTIVATED CELLS OF VASCULAR ENDОTHELIUM IN VITRO AND IN A HUMAN BODY

Abstract. Matrix metalloproteinases (MMP) are structurally related endopeptidase composed of active sites which include ions Zn2+ and Ca2+. Cultured cells of human blood vessels produce MMP-1, proteolytic effect is aimed at splitting the collagen I and III types, and subsequent vascular remodeling. MMP-1 is synthesized as an inactive zymogen proMMP-1. It was shown that interferon alpha, beta and gamma inhibited production by culture of HUVEC proenzyme MMP-1, which seems to characterize their anti-angiogenic action. The effect of immunomodulators is more difficult to explain: perhaps inhibiting effect of imunofan and, as well as activating effect of cycloferon due to their internal structural peculiarities. The action of interferon alpha, beta and gamma, used as HUVEC before infection with HSV-1, and after it led to decrease in production proMMP-1. Apparently, the antiangiogenic effect of IFN is saved in the case of infection of cultures of vascular endothelium with HSV-1. Scatter in the content of proMMP-1 in the serum of blood donors was 1.625–11.8 ng/ml and in patients with chronic microbial-viral infections was 1.22–21.16 ng/ml. Higher rates of proMMP-1 were in older patients group. To estimate the system of MMP in vitro, and in the body a comprehensive study must be conducted, including proMMP-1, the active form of proenzyme and specific inhibitor of MMP-1.

A tissue‐engineered aneurysm model for evaluation of endovascular devices

Endovascular stent grafts used for treatment of arterial aneurysms require preclinical testing for investigation of biological responses following implantation. The preclinical evaluation process related to the safety and efficacy of these devices is limited by the absence of an in vitro aneurysmal blood vessel equivalent capable of providing high-throughput, cost-effective assessments. With this in mind, the focus of this work was to develop an aneurysm model consisting of human blood vessel cells. To create aneurysmal scaffolds, expanded polytetrafluoroethylene vascular grafts were dilated utilizing an angioplasty balloon. Stromal vascular fraction cells isolated from human adipose tissue were integrated with the scaffolds, and luminal flow of nutrient medium was executed for 14 days in a vascular bioreactor. Following bioreactor perfusion, histology verified that a neointimal lining of human tissue had formed. Immunohistochemistry and scanning electron microscopy revealed a flow-contacting layer of smooth muscle cells, characterizing the model as a representation of neointimal formation in an injured or diseased vessel. This study has demonstrated the engineering of a vascular construct containing an aneurysmal dilation. A tissue-engineered aneurysm model could provide an alternative to current nonbiological in vitro aneurysm models and serve as a practical tool in the progression of new devices toward in vivo studies.

In vitro antiangiogenic activity of selective somatostatin subtype‐1 receptor agonists

Endothelial cells of human blood vessels (arteries and veins) show high levels of somatostatin subtype-1 receptor (sst(1)). The aim of the present study is to investigate the inhibitory effects of novel somatostatin analogs, highly selective for human sst(1), on in vitro angiogenesis and their modulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expression. Somatostatin analogs BIM-23745 and BIM-23926 were tested for their ability to prevent proliferation and migration of human endothelial HMEC-1 cells, to modulate VEGF and VEGFR-2 expression and to inhibit sprouting of microvessels from cultured human placental vessel explants in fibrin matrix for 28 days. The somatostatin sst(1 )receptor-selective agonists, BIM-23745 and BIM-23926 showed a suppression of endothelial proliferation (e.g. 10(-6) M BIM-23475, 40.0 +/- 2.1% vs. 100% of controls; 10(-7) M BIM-23926, 55.3 +/- 3.3% vs. 100% of controls), migration (e.g. 10(-7) M BIM-23475, 35.0 +/- 1.56% vs. 100% of controls; 10(-7) M BIM-23926, 53.7 +/- 1.77% vs. 100% of controls) and microvessel sprouting (e.g. 10(-8) M BIM-23475, 42.8 +/- 5.6% vs. 100% of controls; 10(-7) M BIM-23926, 17.2 +/- 11.8% vs. 100% of controls). A small but significant percentage of cells exposed to BIM-23745 and BIM-23926 for 24 h and for 72 h presented typical apoptotic morphology. Moreover, both the analogs significantly inhibit VEGF and VEGFR-2 gene expression in endothelial cells grown for 144 h in a fibrin matrix and the VEGF secretion in conditioned media. The inhibition of endothelial activities suggests potential therapeutic utility for administration of somatostatin sst(1 )receptor-selective agonists in the proliferative diseases involving angiogenesis.

Biomatrix/Polymer Composite Material for Heart Valve Tissue Engineering

Background Decellularized extracellular matrix has been suggested as a scaffold for heart valve tissue engineering or direct implantation. However, cell removal impairs the physical properties of the valve structure and exposes bare collagen fibers that are highly thrombogenic. Matrix/polymer hybrid valves with improved biological and mechanical characteristics may be advantageous. Methods Porcine aortic valves were decellularized enzymatically and impregnated with biodegradable poly(hydroxybutyrate) by a stepwise solvent exchange process. Biocompatibility was tested in vitro using cell proliferation and coagulation assays. Proinflammatory activity was assessed in vivo by implantation of matrix/polymer patches in the rabbit aorta. Biomechanic valve properties and fluid dynamics were tested in a pressure/flow-controlled pulse duplicating system. Matrix/polymer hybrid valves were implanted in pulmonary and aortic position in sheep. Results Biocompatibility assays indicated that human blood vessel cells survive and proliferate on matrix/polymer hybrid tissue. In vitro activation of cellular and plasmatic coagulation cascades was lower than with uncoated control tissue. After implantation in the rabbit aorta, matrix/polymer hybrid patches healed well, with complete endothelialization, mild leukocyte infiltration, and less calcification than control tissue. Matrix/polymer hybrid tissue had superior tensile strength and suture retention strength, and hybrid valves showed good fluid dynamic performance. The two valves in aortic position performed well, with complete endothelialization and limited inflammatory cell invasion after 12 weeks. Of the two valves in pulmonary position, one failed. Conclusions Matrix/polymer hybrid tissue valves have good biological and biomechanic characteristics and may provide superior replacement valves.

Kallistatin is a new inhibitor of angiogenesis and tumor growth

AbstractKallistatin is a unique serine proteinase inhibitor (serpin) and a heparin-binding protein. It has been localized in vascular smooth muscle cells and endothelial cells of human blood vessels, suggesting that kallistatin may be involved in the regulation of vascular function. Our previous study showed that kallistatin plays a role in neointima hyperplasia. In this study, we investigated the potential role of kallistatin in angiogenesis in vitro and in vivo. Purified human kallistatin significantly inhibited vascular endothelial growth factor (VEGF)– or basic fibroblast growth factor (bFGF)–induced proliferation, migration, and adhesion of cultured endothelial cells. Kallistatin attenuated VEGF- or bFGF-induced capillary density and hemoglobin content in subcutaneously implanted Matrigel plugs in mice. To further investigate the role of kallistatin in angiogenesis, we prepared adenovirus carrying the human kallistatin cDNA (Ad.HKBP) and evaluated the effect of kallistatin gene delivery on spontaneous angiogenesis in a rat model of hind-limb ischemia. Local kallistatin gene delivery significantly reduced capillary formation and regional blood perfusion recovery in the ischemic hind limb after removal of the femoral artery. Furthermore, a single intratumoral injection of Ad.HKBP into pre-established human breast tumor xenografts grown in athymic mice resulted in significant inhibition of tumor growth. CD31 immunostaining of tumor sections showed a decreased number of blood vessels in the kallistatin-treated group as compared to the control. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and tumor growth.

High expression of the focal adhesion- and microfilament-associated protein VASP in vascular smooth muscle and endothelial cells of the intact human vessel wall.

The focal adhesion and microfilament-associated protein VASP is a major substrate of both cAMP- and cGMP-dependent protein kinase in intact human platelets. The recent elucidation of the primary VASP structure and identity of VASP binding proteins suggest that VASP is an important component of focal contacts which link signal transduction pathways and elements controlling cell motility. In this study, the high expression of VASP in vascular smooth muscle and endothelial cells of human blood vessels is reported. Western blot and immunofluorescence analysis detected VASP in human heart, femoral artery and a uterine leiomyosarcoma. Within these tissues, smooth muscle cells, small capillaries and the endothelial cell layer were strongly stained by the VASP antiserum. In human heart, an overlapping cellular distribution of the cGMP-dependent protein kinase I (cGK I) and its substrate VASP was noted. Immunoelectron microscopy experiments with vascular smooth muscle cells of the vessel wall revealed that VASP is localized in close proximity to microfilaments, dense plaques and dense bodies. The data of this study and the properties of VASP as a major target of inhibitory vasoactive agents suggest that VASP is an important component which participates in the regulation of cell motility of human vessel wall cells in vivo.