Hypoxia-induced arterial differentiation requires adrenomedullin and notch signaling.

Hypoxia (low oxygen) and Notch signaling are 2 important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increased Notch signaling in a process requiring the vasoactive hormone adrenomedullin.

Heparan sulfation-dependent fibroblast growth factor signaling maintains embryonic stem cells primed for differentiation in a heterogeneous state.

Embryonic stem (ES) cells continuously decide whether to maintain pluripotency or differentiate. While exogenous leukemia inhibitory factor and BMP4 perpetuate a pluripotent state, less is known about the factors initiating differentiation. We show that heparan sulfate (HS) proteoglycans are critical coreceptors for signals inducing ES cell differentiation.

Sp1 mediate hypoxia induced ephrinB2 expression via a hypoxia-inducible factor independent mechanism.

Environmental factors are instrumental in maintaining a healthy vasculature. Oxygen tension is higher in arteries than in veins and thus has the potential to be an instructive signal in arterial/venous specification. EphrinB2 is specifically expressed in arteries and required during embryonic vessel formation.

Characterization of the murine Ephrin-B2 promoter.

Eph/ephrin signaling is pivotal in prenatal angiogenesis. Although their role in these processes has been extensively studied the mechanisms controlling eph/ephrin expression is not fully understood. To better understand the transcriptional regulation of arteriogenesis we have cloned and characterized the promoter of ephrin-B2 and its regulatory elements.

Cardioprotection by hypoxia-inducible factor 1 alpha transfection in skeletal muscle is dependent on haem oxygenase activity in mice.

Aims: The present study investigates whether the cardioprotection achieved by gene delivery of hypoxia-inducible factor-1 alpha (HIF-1 alpha) depends on the downstream factor haem oxygenase (HMOX)-1.

Methods And Results: Immortalized cardiomyocytes (HL-1 cells) were transfected with HIF-1 alpha or HMOX-1 and injured with hydrogen peroxide (H(2)O(2)), and death was evaluated by trypan blue staining. Quadriceps muscles of mice were treated with DNA for HIF-1 alpha and HMOX-1, or sham-treated and electroporated, and 3 days later, hearts were isolated and subjected to global ischaemia and reperfusion.

Functional arterial and venous fate is determined by graded VEGF signaling and notch status during embryonic stem cell differentiation.

Objective: The aim of this work was to develop a mouse embryonic stem (ES) cell system addressing the early specification of the developing vasculature into functional arteries and veins.

Methods And Results: ES cells were differentiated 4 days on collagen-type IV coated dishes to obtain Flk1+ endothelial precursors. Sub-culture of these precursors for additional 4 days robustly generated, in a VEGF dose-dependent manner, mature endothelial cells.