Abstract
Simple SummaryThe control of angiogenesis is essential in disease treatment or regenerative medicine. We conducted a clinical study of dedifferentiated fat (DFAT) cells, a kind of mesenchymal stem cells, by applying cell transplantation therapy to induce angiogenesis in patients with severe ischemic disease. This study aimed to analyze the effect of molecules that regulate angiogenesis in vitro and clarify their molecular mechanisms for therapeutic purposes. Normal human umbilical venous endothelial cells (HUVECs) were cultured in the presence of vascular endothelial growth factor (VEGF). Recombinant human angiopoietin-1-producing cells, conditioned media, mouse DFAT cells, and antioxidant polyphenols were added to this system at various concentrations. After 11 days, the cultures were immunostained with CD31 (PECAM-1), and microscopic images were subjected to analysis (area, length, joint, and path) by using software to quantitatively analyze blood vessel formation. The expression of angiogenic markers and COX pathway genes were analyzed by RT-PCR. As a result, the dose-dependent angiogenesis-promoting effect of rAng-1-producing cells, conditioned medium, or commercially available recombinant Ang-1 were observed. DFAT cells also promoted angiogenesis, whereas polyphenols inhibited angiogenesis in a dose-dependent manner.(1) Background: The control of angiogenesis is essential in disease treatment. We investigated angiogenesis-promoting or -suppressing factors and their molecular mechanisms. (2) Methods: Angiogenesis from HUVECs was quantitatively analyzed using the Angiogenesis Analysis Kit (Kurabo, Osaka, Japan). Human rAng-1-producing 107-35 CHO cells or mouse DFAT-D1 cells were co-cultured with HUVEC. Antioxidant polyphenols were added to the culture. Gene expression was analyzed by RT-PCR. (3) Results: The addition of rAng-1-producing cells, their culture supernatant, or commercially available rAng-1 showed a promoting effect on angiogenesis. The co-culture of DFAT-D1 cells promoted angiogenesis. Polyphenols showed a dose-dependent inhibitory effect on angiogenesis. Luteolin and quercetin showed remarkable anti-angiogenic effects. The expression of vWF, Flk1, and PECAM-1 was increased by adding rAng-1-producing cell culture supernatant. Polyphenols suppressed these genes. Apigenin and luteolin markedly suppressed α-SMA and Flk1. Resveratrol and quercetin enhanced the expression of PPARγ, and luteolin suppressed the expression of COX-1. The expression of endothelial nitric oxide synthase (eNOS), an oxidative stress-related gene, was slightly increased by luteolin. These results suggest that polyphenols induce ROS reduction. (4) Conclusions: We showed the promoting effect of Ang-1 or DFAT and the suppressing effect of polyphenols on angiogenesis and studied their molecular mechanisms. These results help control angiogenesis in regenerative therapy.
Highlights
Vasculogenesis and angiogenesis are the fundamental processes by which new blood vessels are formed
Vasculogenesis is the differentiation of precursor cells into endothelial thecells earliest stage of embryogenesis when mesoderm stemoccurs cells, during endothelial progenitor to form a primitive vascular network
Vascular system is derived from the mesoderm and endothelial is an organ cells that begins forming from vascular remodeling, as hierarchical changes and the retraction of blood vessels, octhe earliest stage ofsuch embryogenesis when mesoderm stem cells, endothelial progenitor curs according to the demand for oxygen and cells (EPCs), are thought to differentiate intonutrients
Summary
Vasculogenesis and angiogenesis are the fundamental processes by which new blood vessels are formed. Angiogenesis cells to Vasculogenesis form a primitiveand vascular network [1]the and mainly occurs during by development. Angiogenesis are fundamental processes which new The blood vascular system is derived from the mesoderm and is an organ that begins forming from vessels are formed. Vasculogenesis is the differentiation of precursor cells into endothelial thecells earliest stage of embryogenesis when mesoderm stemoccurs cells, during endothelial progenitor to form a primitive vascular network [1] and mainly development. Vascular system is derived from the mesoderm and endothelial is an organ cells that begins forming from vascular remodeling, as hierarchical changes and the retraction of blood vessels, octhe earliest stage ofsuch embryogenesis when mesoderm stem cells, endothelial progenitor curs according to the demand for oxygen and cells (EPCs), are thought to differentiate intonutrients
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