Erythropoietin in heart and vessels: focus on transcription and signalling pathways.
Erythropoietin (Epo) is synthesized mainly under hypoxic conditions by renal and extrarenal tissues, including liver, spleen, brain, lung, bone marrow, and reproductive organs. Hypoxia abrogates the degradation of hypoxia-inducible factors (HIF)-1 and -2, that can then bind to the hypoxia response element within the Epo gene, activating its transcription. Receptors for Epo are expressed on cells known to synthesize Epo, but also on cardiomyocytes, cardiac fibroblasts, and endothelial, retinal, gastric, prostate and vascular smooth muscle cells. Epo-receptor binding triggers at least three intracellular signalling cascades: (1) janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5); (2) phosphatidylinositol-3 kinase (PI3K)/Akt, and (3) RAS/mitogen-activated protein kinase (MAPK). Epo also enhances nitric oxide (NO) bioavailability through endothelial NO synthase transcription and activation, and exerts antiapoptotic actions through Bcl-2 and Bcl-XL. NO is a powerful vasodilator, insulin-sensitizer, inhibitor of atherothrombosis and apoptosis, and essential for progenitor mobilization. This article is a concise review of recent advances regarding the molecular and cardiovascular effects of Epo.
Marzo
Francesca
F
Department of Cardiovascular Medicine, University Hospital "A. Gemelli", Rome, Italy.
Lavorgna
Alberto
A
Coluzzi
Giulio
G
Santucci
Eleonora
E
Tarantino
Federica
F
Rio
Teresa
T
Conti
Elena
E
Autore
Camillo
C
Agati
Luciano
L
Andreotti
Felicita
F
D017209:Apoptosis; D004730:Endothelium, Vascular / Q000502:physiology; D004921:Erythropoietin / Q000502:physiology*; D005260:Female; D006321:Heart / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000502:physiology; D017467:Receptors, Erythropoietin / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase