Vascular Endothelial Cell Angiogenesis Research Articles

α2-macroglobulin alleviates glucocorticoid-induced avascular necrosis of the femoral head in mice by promoting proliferation, migration and angiogenesis of vascular endothelial cells

To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX; 10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia

ABSTRACT Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

FRS2 regulated by miR-429 and miR-206 promotes angiogenesis in osteosarcoma

FRS2 has demonstrated oncogenic roles in various malignancies, including liposarcoma and giant cell tumor of bone. However, its role in osteosarcoma remains less understood, and the upstream regulatory molecules influencing FRS2 remain unclear. This study aims to explore the clinical implications and biological function of FRS2 in osteosarcoma, and the potential regulatory microRNAs (miRNAs) governing its expression. Our study indicated significant upregulation of FRS2 in osteosarcoma cells and tissues by Western blotting and immunohistochemical staining. Elevated FRS2 expression correlated positively with increased angiogenesis and poor prognosis, possibly serving as an independent prognostic indicator for osteosarcoma patients. Functional assays revealed that attenuating FRS2 in osteosarcoma cells could mitigate proliferation, migration, and angiogenesis of vascular endothelial cells. Further investigations revealed that miR-429 and miR-206 directly targeted FRS2, exerting a negative regulation on its expression. Furthermore, FRS2 played a role in repressing osteosarcoma advancement influenced by miR-429 or miR-206. In summary, FRS2, influenced by miR-429 and miR-206, emerges as a promising therapeutic candidate for antiangiogenic osteosarcoma treatments.

Glycyl–tRNA Synthetase Induces Psoriasis-Like Skin by Facilitating Skin Inflammation and Vascular Endothelial Cell Angiogenesis

Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA synthetases are universally expressed enzymes that catalyze the first step of protein synthesis. Glycyl-tRNA synthetase (GARS) is a member of the aminoacyl-tRNA synthetase family. In addition to its canonical function, we found that GARS was overexpressed in the serum and skin lesions of patients with psoriasis. Moreover, GARS was highly expressed in human skin keratinocytes, and GARS knockdown in keratinocytes suppressed cell proliferation and promoted apoptosis through NF-κB/MAPK signaling pathway. Moreover, intradermal injection of recombinant GARS protein caused skin thickening, angiogenesis, and IFN/TNF-driven skin inflammation. Intriguingly, the reported functional receptor for GARS, cadherin 6 (CDH6), was specifically expressed in vascular endothelial cells, and we found that keratinocyte-derived GARS promotes inflammation and angiogenesis of vascular endothelial cells through CDH6. In addition, intradermal injection of GARS aggravated the phenotype and angiogenesis in imiquimod-induced psoriasiform dermatitis models, whereas the psoriatic phenotype and angiogenesis were relieved after knockdown of GARS by adeno-associated virus. Taken together, the results of this study identify the critical role of GARS in the pathogenesis of psoriasis and suggest that blocking GARS may be a therapeutic approach for alleviating psoriasis.

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer.

Hypoxia can lead to different responses from cancer cells, including cell death or survival, partially depending on how long it is exposed. Patients with cancer and under hypoxic tumour conditions have a poorer prognosis and are at greater risk of metastasis. Physiological response to low oxygen levels is controlled by hypoxia-inducible factor (HIF)-1. Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF). In addition, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia. One of the most compelling features that drive continued interest in curcumin is the molecules' modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours. In this review, we discuss the role of curcumin in modulating hypoxia and investigate the mechanisms and regulatory factors of hypoxia in tumour tissues.

Calcitonin gene-related peptide: a potential protective agent in cerebral ischemia-reperfusion injury.

Ischemic stroke is the most common type of cerebrovascular disease with high disability and mortality rates, which severely burdens patients, their families, and society. At present, thrombolytic therapy is mainly used for the treatment of ischemic strokes. Even though it can achieve a good effect, thrombolytic recanalization can cause reperfusion injury. Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays a neuroprotective role in the process of ischemia-reperfusion injury. By combining with its specific receptors, CGRP can induce vasodilation of local cerebral ischemia by directly activating the cAMP-PKA pathway in vascular smooth muscle cells and by indirectly activating the NO-cGMP pathway in an endothelial cell-dependent manner,thus rapidly increasing ischemic local blood flow together with reperfusion. CGRP, as a key effector molecule of neurogenic inflammation, can reduce the activation of microglia, downregulates Th1 classical inflammation, and reduce the production of TNF-α, IL-2, and IFN-γ and the innate immune response of macrophages, leading to the reduction of inflammatory factors. CGRP can reduce the overexpression of the aquaporin-4 (AQP-4) protein and its mRNA in the cerebral ischemic junction, and play a role in reducing cerebral edema. CGRP can protect endothelial cells from angiotensin II by reducing the production of oxidants and protecting antioxidant defense. Furthermore, CGRP-upregulated eNOS can further induce VEGF expression, which then promotes the survival and angiogenesis of vascular endothelial cells. CGRP can also reduce apoptosis by promoting the expression of Bcl-2 and inhibiting the expression of caspase-3. These effects suggest that CGRP can reduce brain injury and repair damaged nerve function. In this review, we focused on the role of CGRP in cerebral ischemia-reperfusion injury.

The proliferation and angiogenesis in hemangioma-derived endothelial cells is affected by STC2 medicated VEGFR2/Akt/eNOS pathway.

Stanniocalcin-2 (STC2), a secreted glycoprotein that is involved in the regulation of angiogenesis, was proposed as one of the mechanisms of neovascularization in hemangioma (HA). We aimed to investigate the effect of STC2 on proliferation and angiogenesis in hemangioma-derived endothelial cells. The hemangioma samples from HA patients with the median age of six months were surgically collected in the Affiliated Hospital of Weifang Medical University from October 2019 to June 2021, and divided into normal skin tissues (n=10), involuting-phase HAs (n=10) and proliferating-phase HAs (n=10) according to the Mulliken classification. The expression of STC2 was detected in involuting-phase HAs and proliferating-phase HAs. Hemangioma endothelial cells (HemEC) were transfected with small interfering RNA (siRNA) specific for STC2, and cell survival and tube formation were analyzed. STC2 expression in proliferating-phase HAs was markedly higher than in the normal skin tissues and involving-phase HAs. Similarly, STC2 expression was higher in HemEC compared to the control human umbilical vein endothelial cells (HUVEC). Knockdown of STC2 slowed the proliferation of HemEC and decreased the expression of proliferating cell nuclear antigen (PCNA) in HemEC. Moreover, knockdown of STC2 in HemEC inhibited vascular endothelial cell angiogenesis and regulated the expression and phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). Mechanistically, STC2 knockdown attenuated the activation of Akt/eNOS signaling, which was abolished by insulin growth factor-1 (IGF-1), the activator of Akt signaling, accompanying by increased proliferation and tube formation of HemEC. Inhibition of STC2 suppresses HemEC proliferation and angiogenesis by VEGFR2/Akt/eNOS pathway, which warrants further development of STC2-based strategies for HA treatment.

Gallic acid-modified bioglass with combined photothermal and antibacterial effects for the regeneration of infected diabetic wound

Diabetes-associated chronic wound management has been a serious worldwide issue, which is obstructed by multiple factors such as sustained inflammation, attenuated angiogenesis, and fragile defense against bacterial infection in the wound niche. Thus, there stands an urgent demand for biomaterial dressings that are able to treat such complex conditions. Herein, we developed a composite biomaterial of gallic acid-modified bioglass (GA@BG) in an anhydrous system, by using two agents which have already been used in clinical practice. The prepared GA@BG not merely promoted the migration and angiogenesis of vascular endothelial cells but also provided superior antibacterial performance in the local environment. Significantly, the gallic acid-assisted modification made the color of bioglass (BG) change from white to black, endowing it with high light absorption to successfully achieve a significant photothermal property. Then, the strengthened antibacterial effects were further realized by irradiation with near-infrared light (NIR) based on this photothermal property. Particularly, the combined therapy (GA@BG + NIR) was demonstrated as an effective strategy in treating the infected full-thickness dermal wounds of diabetic rats. This research provides a convenient non-antibiotic medicine formula for diabetic wounds with infection, and demonstrates a valid modification for inorganic bioglass-based material with organic polyphenol, which inspires more expansive composites for wound biomaterials.

Downregulation of miR-210-3p Attenuates High Glucose-Induced Angiogenesis of Vascular Endothelial Cells via Targeting FGFRL1

Introduction: Vascular endothelial cell injury and angiogenesis induced by hyperglycemia are the main pathological basis of vascular complications in diabetes mellitus. Our study aimed to investigate the role and mechanism of miR-210-3p in high glucose (HG)-induced angiogenesis. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with HG to mimic the pathological process of hyperglycemia. HUVECs were divided into the control group, HG group, HG+inhibitor-NC group, and HG+miR-210-3p inhibitor group. Proliferation and migration were tested by wound healing assay, tube formation, and Transwell assay. Quantitation real-time PCR and Western blots were performed to determine the expression of miR-210-3p and relative proteins, respectively. Results: The level of miR-210-3p significantly increased in HUVECs treated by HG. The knockdown of miR-210-3p attenuated the tube formation, proliferation, and migration of cultured HUVECs in vitro to inhibit angiogenesis by increasing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) and then attenuating the phosphorylation of signal transducer and activator of transcription 3 (STAT3), extracellular regulated protein kinases, and protein kinase B (Akt). Conclusion: Our study revealed that miR-210-3p might be a promising target for treating diabetic-associated vascular injury.

Angiogenesis-Browning Interplay Mediated by Asprosin-Knockout Contributes to Weight Loss in Mice with Obesity.

Asprosin (ASP) is a recently identified adipokine secreted by white adipose tissue (WAT). It plays important roles in the maintenance of glucose homeostasis in the fasting state and in the occurrence and development of obesity. However, there is no report on whether and how ASP would inhibit angiogenesis and fat browning in the mouse adipose microenvironment. Therefore, the study sought to investigate the effects of ASP-knockout on angiogenesis and fat browning, and to identify the interaction between them in the ASP-knockout mouse adipose microenvironment. In the experiments in vivo, the ASP-knockout alleviated the obesity induced by a high fat diet (HFD) and increased the expressions of the browning-related proteins including uncoupling protein 1 (UCP1), PRD1-BF-1-RIZ1 homologus domain-containing protein-16 (PRDM16) and PPAR gamma coactivator 1 (PGC1-α) and the endothelial cell marker (CD31). In the experiments in vitro, treatment with the conditional medium (CM) from ASP-knockout adipocytes (ASP-/--CM) significantly promoted the proliferation, migration and angiogenesis of vascular endothelial cells, and increased the expressions of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) pathway proteins. In addition, the treatment with CM from endothelial cells (EC-CM) markedly reduced the accumulation of lipid droplets and increased the expressions of the browning-related proteins and the mitochondrial contents. Moreover, the treatment with EC-CM significantly improved the energy metabolism in 3T3-L1 adipocytes. These results highlight that ASP-knockout can promote the browning and angiogenesis of WAT, and the fat browning and angiogenesis can interact in the mouse adipose microenvironment, which contributes to weight loss in the mice with obesity.

Collaborative Design of MgO/FeOx Nanosheets on Titanium: Combining Therapy with Regeneration.

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2 O2 , which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.

Effects and mechanism of human umbilical vein endothelial cells-derived exosomes on wound healing in diabetic rabbits

Effects and mechanism of human umbilical vein endothelial cells-derived exosomes on wound healing in diabetic rabbits

Toll-like Receptor 2 Is Associated with the Immune Response, Apoptosis, and Angiogenesis in the Mammary Glands of Dairy Cows with Clinical Mastitis.

Toll-like receptor 2 (TLR2) plays a crucial role in bacterial recognition and the host immune response during infection. However, its function and downstream biological processes (BPs) in the mammary glands (MGs) of Holstein cows with clinical mastitis (CM) are not fully understood. This study aimed to comprehensively identify the BPs and differentially expressed proteins (DEPs) associated with the bacterial response and TLR2 using data-independent acquisition (DIA) proteomic data. A possible mechanism for the action of TLR2 was proposed, and the results suggested that the expression levels of TLR2 and caspase 8 (CASP8) were positively correlated with the apoptosis of MGs. The expression patterns of TLR2 and TEK receptor tyrosine kinase 2 (Tie2) were negatively correlated with angiogenesis. These results indicated that TLR2 might promote apoptosis in mammary epithelial cells (MECs) and vascular endothelial cells (VECs) via upregulation of CASP8 expression, and inhibition of angiogenesis in VECs via downregulation of Tie2 expression in dairy cows with CM. In conclusion, TLR2 is associated with inflammation, apoptosis, and angiogenesis in the MGs of dairy cows with bacteria-induced mastitis. These results contribute to a deeper understanding of the pathogenic mechanisms and provide the knowledge needed for developing the prevention and treatment of dairy mastitis.

Coaxially Fabricated Dual‐Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration (Adv. Healthcare Mater. 16/2022)

Controlled Drug Release In article 2200571, Min Zhu, Xudong Wang, Kaili Lin and co-workers fabricate a novel dual-drug loading coaxially electrospinning fibrous mat with programmed release behavior. The early and rapid release of angiogenesis-promoting drug deferoxamine promotes the angiogenesis of vascular endothelial cells and the sustained release of osteogenesis-inducing drug dexamethasone enhances osteogenesis of bone mesenchymal stem cells, and synergistically boosts vascularized bone regeneration.

Acellular dermal matrix decorated with collagen-affinity peptide accelerate diabetic wound healing through sustained releasing Histatin-1 mediated promotion of angiogenesis

Treating diabetic ulcers is a major challenge in clinical practice, persecuting millions of patients with diabetes and increasing the medical burden. Recombinant growth factor application can accelerate diabetic wound healing via angiogenesis. The local administration of recombinant growth factors has no robust clinical efficiency because of the degradation of append short duration of the molecules in the hostile inflammatoryenvironment.The present study focused on the pathophysiology of impaired neovascularization and growth factor short duration in the diabetic wound. We prepared a collagen-binding domain (CBD)-fused recombinant peptide (C-Histatin-1) that had both pro-angiogenesis capacity and collagen-affinity properties. Next, we created a biocompatible acellular dermal matrix (ADM) as a drug delivery carrier that featured collagen-richness, high porosity, and non-cytotoxicity. C-Histatin-1 was then tethered on ADM to obtain a sustained-release effect. Finally, a functional scaffold (C-Hst1/ADM) was developed. C-Hst1/ADM can sustain-release Histatin-1 to promote the adhesion, migration, and angiogenesisof vascular endothelial cells in vitro. Using a diabetic wound model, we showed that C-Hst1/ADM could significantly promote angiogenesis, reduce scar widths, and improve extracellular collagen accumulation. Therefore, the results of this study provide a foundation for the clinical application of C-Hst1/ADM covering scaffold in the treatment of diabetic wounds.

Yeast beta-glucan mediates histone deacetylase 5-induced angiogenesis in vascular endothelial cells

The role of yeast-derived β-glucan in angiogenesis has not been elucidated because there have been few specific studies on its clinical and physiological significance. Therefore, this study investigated the correlation between β-glucan and histone deacetylase 5 (HDAC5) in human umbilical vein endothelial cells (HUVECs), revealing the role of β-glucan in angiogenesis. We confirmed that HDAC5 was phosphorylated by β-glucan stimulation and released from the nucleus to the cytoplasm. Furthermore, we found that β-glucan-stimulated HDAC5 translocation mediates the transcriptional activation of MEF2. As a result, the expression of KLF2, EGR2, and NR4A2, whose expression is MEF2-dependent and involved in angiogenesis, increased. Thus, we showed the activity of β-glucan in angiogenesis through in vitro and ex vivo assays including cell migration, tube formation, and aortic ring analyses. Specifically, application of an HDAC5 inhibitor repressed MEF2 transcriptional activation in both in vitro and ex vivo angiogenesis. HDAC5 inhibitor LMK235 inhibited the proangiogenic activity of beta-glucan, suggesting that β-glucan induces angiogenesis through HDAC5. These findings suggest that HDAC5 is essential for angiogenesis, and that β-glucan induces angiogenesis. In conclusion, this study demonstrates that β-glucan induces angiogenesis through HDAC5. It also suggests that β-glucan has potential value as a novel therapeutic agent for modulating angiogenesis.

Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma.

Cancer stemness evinces interest owing to the resulting malignancy and poor prognosis. We previously demonstrated that hepatic stem cell-like hepatocellular carcinoma (HpSC-HCC) is associated with high vascular invasion and poor prognosis. Dickkopf-1 (DKK-1), a Wnt signaling regulator, is highly expressed in HpSC-HCC. Here, we assessed the diagnostic and prognostic potential of serum DKK-1. Its levels were significantly higher in 391 patients with HCC compared with 205 patients with chronic liver disease. Receiver operating characteristic curve analysis revealed the optimal cutoff value of DKK-1 to diagnose HCC and predict the 3-year survival as 262.2 and 365.9 pg/mL, respectively. HCC patients with high-serum DKK-1 levels showed poor prognosis. We evaluated the effects of anti-DKK-1 antibody treatment on tumor growth in vivo and of recombinant DKK-1 on cell proliferation, invasion, and angiogenesis in vitro. DKK-1 knockdown decreased cancer cell proliferation, migration, and invasion. DKK-1 supplementation promoted angiogenesis in vitro; this effect was abolished by an anti-DKK-1 antibody. Co-injection of the anti-DKK-1 antibody with Huh7 cells inhibited their growth in NOD/SCID mice. Thus, DKK-1 promotes proliferation, migration, and invasion of HCC cells and activates angiogenesis in vascular endothelial cells. DKK-1 is a prognostic biomarker for HCC and a functional molecule for targeted therapy.

Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Effects of biomimetic hydroxyapatite coatings on osteoimmunomodulation

Macrophages play a very fundamental role in bone regeneration. Changing the physicochemical properties of biomaterials to regulate the genes and protein expressions of Macrophages in vivo is of great significance to promote osteogenesis and angiogenesis in bone tissue engineering. Herein, we investigated the interaction of biomimetic hydroxyapatite coatings with macrophages and the subsequent impact on osteogenesis and angiogenesis. In this study, we found that biomimetic hydroxyapatite coating could inhibit the expression of inflammatory factors (tumor necrosis factor-α, TNF-α) while promoting bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), thereby promoting angiogenesis of vascular endothelial cells and osteogenic differentiation of mesenchymal stem cells. This study demonstrated that biomimetic hydroxyapatite coating modified polycaprolactone (PCL) possessed an excellent osteoimmunomodulatory property and was a promising coating material for the application.

Biphasic Effect of Pirfenidone on Angiogenesis.

Pirfenidone (PFD), a synthetic arsenic compound, has been found to inhibit angiogenesis at high concentrations. However, the biphasic effects of different PFD concentrations on angiogenesis have not yet been elucidated, and the present study used an in vitro model to explore the mechanisms underlying this biphasic response. The effect of PFD on the initial angiogenesis of vascular endothelial cells was investigated through a Matrigel tube formation assay, and the impact of PFD on endothelial cell migration was evaluated through scratch and transwell migration experiments. Moreover, the expression of key migration cytokines, matrix metalloproteinase (MMP)-2 and MMP-9, was examined. Finally, the biphasic mechanism of PFD on angiogenesis was explored through cell signaling and apoptosis analyses. The results showed that 10–100 μM PFD has a significant and dose-dependent inhibitory effect on tube formation and migration, while 10 nM–1 μM PFD significantly promoted tube formation and migration, with 100 nM PFD having the strongest effect. Additionally, we found that a high concentration of PFD could significantly inhibit MMP-2 and MMP-9 expression, while low concentrations of PFD significantly promoted their expression. Finally, we found that high concentrations of PFD inhibited EA.hy926 cell tube formation by promoting apoptosis, while low concentrations of PFD promoted tube formation by increasing MMP-2 and MMP-9 protein expression predominantly via the EGFR/p-p38 pathway. Overall, PFD elicits a biphasic effect on angiogenesis through different mechanisms, could be used as a new potential drug for the treatment of vascular diseases.