Redox Signaling of Angiogenesis

Maulik, Nilanjana

doi:10.1089/152308602760598963

Cited by 210 publications

(202 citation statements)

References 88 publications

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“…However, here we demonstrated that changing the media could also cause fluctuations in DO levels; for instance, media replacement after 24 h reoxygenated the cells, which was previously shown to have crucial effects on cellular responses, including angiogenesis (30,47). Previous studies have reported the values of V max and K m of HUVECs at various cell-seeding densities (15,42).…”

Section: C435 Oscillations In Dissolved Oxygen During Tubulogenesismentioning

confidence: 51%

Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels

Abaci

Truitt

Tan

et al. 2011

American Journal of Physiology-Cell Physiology

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The availability of oxygen (O2) is a critical parameter affecting vascular tube formation. In this study, we hypothesize that dissolved oxygen (DO) levels in collagen gels change during the three-dimensional (3D) culture of human umbilical vein endothelial cells (HUVECs) in atmospheric conditions and that such changes affect the kinetics of tube formation through the production of reactive oxygen species (ROS). We demonstrate a decrease in O2 tension during 3D cultures of HUVECs. Noninvasive measurements of DO levels during culture under atmospheric conditions revealed a profound decrease that reached as low as 2% O2 at the end of 24 h. After media replacement, DO levels rose rapidly and equilibrated at ϳ15% O 2, creating a reoxygenated environment. To accurately estimate DO gradients in 3D collagen gels, we developed a 3D mathematical model and determined the Michaelis-Menten parameters, V max and K m, of HUVECs in collagen gels. We detected an increase in ROS levels throughout the culture period. Using diphenyliodonium to inhibit ROS production resulted in the complete inhibition of tube formation. Interference RNA studies further showed that hypoxiainducible factors (HIFs)-1␣ and -2␣ are not involved in the formation of 3D tubes in collagen gels. We conclude that ROS affect the tubulogenesis process through HIF␣-independent pathways, where the levels of ROS are influenced by the uncontrolled variations in DO levels. This study is the first demonstration of the critical and unexpected role of O 2 during 3D in vitro culture models of tubulogenesis in atmospheric conditions. microvasculature; reactive oxygen species; hypoxia-inducible factors AN UNDERSTANDING OF THE MECHANISMS controlling how blood vessels form from endothelial cells (ECs) is crucial for developmental biology and vascular tissue engineering. In recent decades, our understanding of the molecular regulation underlying vascular development has vastly expanded, primarily because of newly available, well-defined in vitro models. One common model is the culturing of ECs in gels made of the extracellular matrix component collagen, which has enabled us to investigate the effects of many factors on tubulogenesis (24,38,39).The availability of oxygen (O 2 ) is a critical parameter affecting how vascular cells form tubes. In vitro models have demonstrated that hypoxic conditions enhance tube formation, as do hypoxic regions formed by the O 2 consumption of the cells in threedimensional (3D) structures (3,19,32). Research has shown that the rate of O 2 consumption of cells follows the Michaelis-Menten kinetics and depends on the cell type, cell density (15), and dissolved oxygen (DO) levels (1). Variations in DO levels strongly affect angiogenesis (19, 48) through different vascular cell responses, such as viability, differentiation, migration, and remodeling of the extracellular matrix (4, 27, 40).Hypoxia-inducible factors (HIFs) and reactive oxygen species (ROS) are among the effectors responsible for cellular responses to changing DO levels. HIF1␣ and HI...

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Section: C435 Oscillations In Dissolved Oxygen During Tubulogenesismentioning

confidence: 51%

Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels

Abaci

Truitt

Tan

et al. 2011

American Journal of Physiology-Cell Physiology

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“…Additionally, transcription of several gene classes, including cytokines, matrix proteins and hormones, are modulated by NO regulation of nuclear factor κB (NFκB), hypoxia inducible factor 1 (HIF1) and zinc-finger transcription factors (Huang et al, 1999b;Kroncke and Carlberg, 2000;Matthews et al, 1996;Tabuchi et al, 1996;Torres and Forman, 2000). ROS, however, regulates transcription of protein kinases, growth factors and transcription factors, and plays a role in signaling in the vasculature (Burdon, 1996;Giaccia and Kastan, 1998;Maulik, 2002;Meyer et al, 1994;Nose, 2000). Additionally, ROS inhibits low molecular weight (LMW) phosphatases, which have been shown to downregulate proliferation by attenuating growth factor receptor signaling (Chiarugi, 2001;Huang et al, 1999a).…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

et al. 2004

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Nitric oxide (NO) has been demonstrated to mediate events during ovulation,pregnancy, blastocyst invasion and preimplantation embryogenesis. However,less is known about the role of NO during postimplantation development. Therefore, in this study, we explored the effects of NO during vascular development of the murine yolk sac, which begins shortly after implantation. Establishment of the vitelline circulation is crucial for normal embryonic growth and development. Moreover, functional inactivation of the endodermal layer of the yolk sac by environmental insults or genetic manipulations during this period leads to embryonic defects/lethality, as this structure is vital for transport, metabolism and induction of vascular development. In this study, we describe the temporally/spatially regulated distribution of nitric oxide synthase (NOS) isoforms during the three stages of yolk sac vascular development (blood island formation, primary capillary plexus formation and vessel maturation/remodeling) and found NOS expression patterns were diametrically opposed. To pharmacologically manipulate vascular development,an established in vitro system of whole murine embryo culture was employed. During blood island formation, the endoderm produced NO and inhibition of NO(L-NMMA) at this stage resulted in developmental arrest at the primary plexus stage and vasculopathy. Furthermore, administration of a NO donor did not cause abnormal vascular development; however, exogenous NO correlated with increased eNOS and decreased iNOS protein levels. Additionally, a known environmental insult (high glucose) that produces reactive oxygen species(ROS) and induces vasculopathy also altered eNOS/iNOS distribution and induced NO production during yolk sac vascular development. However, administration of a NO donor rescued the high glucose induced vasculopathy, restored the eNOS/iNOS distribution and decreased ROS production. These data suggest that NO acts as an endoderm-derived factor that modulates normal yolk sac vascular development, and decreased NO bioavailability and NO-mediated sequela may underlie high glucose induced vasculopathy.

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“…Both VEGF and eNOS are up-regulated in situations of increased oxidative stress [51,52]. Therefore, one hypothesis for the observed effects of B vitamins in this study may be through the modulation of oxidative stress following the induction of ischemia.…”

Section: Discussionmentioning

confidence: 63%

Impaired recovery of hind limb muscle perfusion following ischemic injury in rodents receiving B vitamin supplementation

Lee¹,

Desjardins²,

Sorokin³

et al. 2017

Blood Heart Circ

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Redox Signaling of Angiogenesis

Cited by 210 publications

References 88 publications

Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels

Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

Impaired recovery of hind limb muscle perfusion following ischemic injury in rodents receiving B vitamin supplementation

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