Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo

Daniela Sorriento, Gaetano Santulli, Carmine Del Giudice, Antonio Anastasio, Bruno Trimarco, Guido Iaccarino

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Recently it has been demonstrated that catecholamines are produced and used by macrophages and mediate immune response. The aim of this study is to verify whether endothelial cells (ECs), which are of myeloid origin, can produce catecholamines. We demonstrated that genes coding for tyrosine hydroxylase, Dopa decarboxylase, dopamine β hydroxylase (DβH), and phenylethanolamine- iV-methyl transferase, enzymes involved in the synthesis of catecholamines, are all expressed in basal conditions in bovine aorta ECs, and their expression is enhanced in response to hypoxia. Moreover, hypoxia enhances catecholamine release. To evaluate the signal transduction pathway that regulates catecholamine synthesis in ECs, we overexpressed in bovine aorta ECs either protein kinase A (PKA) or the transcription factor cAMP response element binding, because PKA/cAMP response element binding activation induces tyrosine hydroxylase transcription and activity in response to stress. Both cAMP response element binding and PKA overexpression enhance DβH and phenylethanolamine-iV-methyl transferase gene expression and catecholamine release, whereas H89, inhibitor of PKA, exerts the opposite effect, evidencing the role of PKA/cAMP response element binding transduction pathway in the regulation of catecholamine release in bovine aorta ECs. We then evaluated by immunohistochemistry the expression of tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine-iV-methyl transferase in femoral arteries from hindlimbs of C57Bl/6 mice 3 days after removal of the common femoral artery to induce chronic ischemia. Ischemia evokes tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine-iV-methyl transferase expression in the endothelium. Finally, the pharmacological inhibition of catecholamine release by fusaric acid, an inhibitor of DβH, reduces the ability of ECs to form network-like structures on Matrigel matrix. In conclusion, our study demonstrates for the first time that ECs are able to synthesize and release catecholamines in response to ischemia.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalHypertension
Volume60
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • Angiogenesis
  • Catecholamines
  • Endothelium
  • Ischemia

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Sorriento, D., Santulli, G., Del Giudice, C., Anastasio, A., Trimarco, B., & Iaccarino, G. (2012). Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo. Hypertension, 60(1), 129-136. https://doi.org/10.1161/HYPERTENSIONAHA.111.189605