Neovasculogenic Effect of 11,12-epoxyeicosatrienoic Acid Involves the Akt/eNOS Signaling Pathways in Human Endothelial Progenitor Cells

Overview

Journal Biomedicine (Taipei)

Specialty Biomedical Engineering

Date 2022 Nov 16

PMID 36381190

Authors

Hung-Chang Hung

Jia-Ning Syu

Che-Yi Chao

Shu-Ming Huang

Cheng-Chieh Lin

Mei-Due Yang

Shu-Yao Tsai

Feng-Yao Tang

Affiliations

Soon will be listed here.

Abstract

The 11,12-epoxy-eicosatrienoic acid (11,12-EET) is formed from arachidonic acid (AA) by cytochrome P450 2J2 (CYP 2J2) epoxygenase and function as an effector in blood vessels. Human endothelial progenitor cells (hEPCs), a preceding cell source for endothelial cells (ECs), involve in the vascular tissue repairing by postnatal neovasculogenesis. However, the effect of 11, 12-EET on hEPCs and neovasculogenesis is not well known. In the current study, we examined the function of 11, 12-EET in hEPCs-mediated neovasculogenesis by using tubular formation analysis, Western Blotting assay, immunofluorescence staining, flow cytometry analysis and zymogram analysis. The results suggest that 11, 12-EET significantly induces neovasculogenesis through the phosphorylation of phosphoinositide 3-kinase (PI3-K)/Akt, endothelial-nitric oxide synthase (e-NOS) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways. 11, 12-EET up-regulates the expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and nuclear factor kappa B (NF-κB) proteins. Moreover, 11, 12-EET augments the expression of VE-cadherin and CD31 proteins in hEPCs. 11, 12-EET also augmented Rac1/Rho A signaling cascades, cell migration and an up-regulation of matrix metalloproteinase (MMP) -2 and -9 proteins. These results demonstrate that 11, 12-EET exerts a significant function in the neovasculogenesis of hEPCs.

Citing Articles

The plasma lipids with different fatty acid chains are associated with the risk of hemorrhagic stroke: a Mendelian randomization study.

Zhang X, Zhu X, Shi Q Front Neurol. 2024; 15:1432878.

PMID: 39139767 PMC: 11319180. DOI: 10.3389/fneur.2024.1432878.

References

Peters E . Endothelial Progenitor Cells for the Vascularization of Engineered Tissues. Tissue Eng Part B Rev. 2017; 24(1):1-24. PMC: 5797330. DOI: 10.1089/ten.TEB.2017.0127. View

Kanayasu-Toyoda T, Tanaka T, Kikuchi Y, Uchida E, Matsuyama A, Yamaguchi T . Cell-Surface MMP-9 Protein Is a Novel Functional Marker to Identify and Separate Proangiogenic Cells from Early Endothelial Progenitor Cells Derived from CD133(+) Cells. Stem Cells. 2016; 34(5):1251-62. DOI: 10.1002/stem.2300. View

Tang F, Chiang E, Shih C . Green tea catechin inhibits ephrin-A1-mediated cell migration and angiogenesis of human umbilical vein endothelial cells. J Nutr Biochem. 2006; 18(6):391-9. DOI: 10.1016/j.jnutbio.2006.07.004. View

Takizawa S, Nagata E, Nakayama T, Masuda H, Asahara T . Recent Progress in Endothelial Progenitor Cell Culture Systems: Potential for Stroke Therapy. Neurol Med Chir (Tokyo). 2016; 56(6):302-9. PMC: 4908073. DOI: 10.2176/nmc.ra.2016-0027. View

Borgel J, Bulut D, Hanefeld C, Neubauer H, Mugge A, Epplen J . The CYP2J2 G-50T polymorphism and myocardial infarction in patients with cardiovascular risk profile. BMC Cardiovasc Disord. 2008; 8:41. PMC: 2626571. DOI: 10.1186/1471-2261-8-41. View

Panigrahy D, Edin M, Lee C, Huang S, Bielenberg D, Butterfield C . Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest. 2011; 122(1):178-91. PMC: 3248288. DOI: 10.1172/JCI58128. View

Rana D, Kumar A, Sharma S . Endothelial Progenitor Cells as Molecular Targets in Vascular Senescence and Repair. Curr Stem Cell Res Ther. 2018; 13(6):438-446. DOI: 10.2174/1574888X13666180502100620. View

Webler A, Michaelis U, Popp R, Barbosa-Sicard E, Murugan A, Falck J . Epoxyeicosatrienoic acids are part of the VEGF-activated signaling cascade leading to angiogenesis. Am J Physiol Cell Physiol. 2008; 295(5):C1292-301. PMC: 2584984. DOI: 10.1152/ajpcell.00230.2008. View

Tang F, Nguyen N, Meydani M . Green tea catechins inhibit VEGF-induced angiogenesis in vitro through suppression of VE-cadherin phosphorylation and inactivation of Akt molecule. Int J Cancer. 2003; 106(6):871-8. DOI: 10.1002/ijc.11325. View

10.

Zhou J, Cheng M, Liao Y, Hu Y, Wu M, Wang Q . Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells. PLoS One. 2013; 8(5):e63126. PMC: 3660394. DOI: 10.1371/journal.pone.0063126. View

11.

Akhshi T, Wernike D, Piekny A . Microtubules and actin crosstalk in cell migration and division. Cytoskeleton (Hoboken). 2013; 71(1):1-23. DOI: 10.1002/cm.21150. View

12.

Sommer K, Jakob H, Badjlan F, Henrich D, Frank J, Marzi I . 11,12 and 14,15 epoxyeicosatrienoic acid rescue deteriorated wound healing in ischemia. PLoS One. 2019; 14(1):e0209158. PMC: 6335021. DOI: 10.1371/journal.pone.0209158. View

13.

Schwartzman M, Ferreri N, Carroll M, Songu-Mize E, McGiff J . Renal cytochrome P450-related arachidonate metabolite inhibits (Na+ + K+)ATPase. Nature. 1985; 314(6012):620-2. DOI: 10.1038/314620a0. View

14.

Bachelier K, Bergholz C, Friedrich E . Differentiation potential and functional properties of a CD34‑CD133+ subpopulation of endothelial progenitor cells. Mol Med Rep. 2019; 21(1):501-507. DOI: 10.3892/mmr.2019.10831. View

15.

Hahner F, Moll F, Schroder K . NADPH oxidases in the differentiation of endothelial cells. Cardiovasc Res. 2019; 116(2):262-268. DOI: 10.1093/cvr/cvz213. View

16.

Spiecker M, Darius H, Hankeln T, Soufi M, Sattler A, Schaefer J . Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation. 2004; 110(15):2132-6. PMC: 2633457. DOI: 10.1161/01.CIR.0000143832.91812.60. View

17.

Kim K, Meng Y, Kim J, Baek E, Suh W . Direct and differential effects of stem cell factor on the neovascularization activity of endothelial progenitor cells. Cardiovasc Res. 2011; 92(1):132-40. DOI: 10.1093/cvr/cvr161. View

18.

Meng S, Cao J, Zhang X, Fan Y, Fang L, Wang C . Downregulation of microRNA-130a contributes to endothelial progenitor cell dysfunction in diabetic patients via its target Runx3. PLoS One. 2013; 8(7):e68611. PMC: 3709913. DOI: 10.1371/journal.pone.0068611. View

19.

Liu X, Li Y, Liu Y, Luo Y, Wang D, Annex B . Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy. Am J Pathol. 2009; 176(1):504-15. PMC: 2797908. DOI: 10.2353/ajpath.2010.081152. View

20.

Asahara T, Isner J . Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res. 2002; 11(2):171-8. DOI: 10.1089/152581602753658385. View