Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells.

Oxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available about the interaction between NOX5 homolog-derived and the PG pathway in the cardiovascular context. Our main goal was to characterize NOX5-derived duanyu1670 effects in PG homeostasis and their potential relevance in cardiovascular pathologies. For that purpose, two experimental systems were employed: an adenoviral NOX5-β overexpression model in immortalized human aortic endothelial cells (TeloHAEC) and a chronic infarction in vivo model developed from a conditional endothelial NOX5 knock-in mouse. NOX5 increased cyclooxygenase-2 isoform (COX-2) expression and prostaglandin E₂ (PGE₂) production through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in TeloHAEC. Protein kinase C activation and intracellular calcium level (Ca⁺⁺) mobilization increased duanyu1670 production and NOX5 overexpression, which promoted a COX-2/PGE₂ response in vitro. In the chronic infarction model, mice encoding endothelial NOX5 enhanced the cardiac mRNA expression of COX-2 and PGES, suggesting a COX-2/PGE₂ response to NOX5 presence in an ischemic situation. Our data support that NOX5-derived duanyu1670 may modulate the COX-2/PGE₂ axis in endothelial cells, which might play a relevant role in the pathophysiology of heart infarction.

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