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Lee, Candace Y.W.; Huntley, Brenda K; Burnett, John C

Cyclic GMP stimulating actions of a novel fully humanized designer natriuretic peptide, CBB‐NP, in human aortic endothelial cells as compared to the native natriuretic peptides

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  • Medientyp: E-Artikel
  • Titel: Cyclic GMP stimulating actions of a novel fully humanized designer natriuretic peptide, CBB‐NP, in human aortic endothelial cells as compared to the native natriuretic peptides
  • Beteiligte: Lee, Candace Y.W.; Huntley, Brenda K; Burnett, John C
  • Erschienen: Wiley, 2009
  • Erschienen in: The FASEB Journal
  • Sprache: Englisch
  • DOI: 10.1096/fasebj.23.1_supplement.932.10
  • ISSN: 1530-6860; 0892-6638
  • Schlagwörter: Genetics ; Molecular Biology ; Biochemistry ; Biotechnology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Background</jats:title><jats:p>CBB‐NP is a novel fully humanized designer natriuretic peptide (NP) integrating the 17‐amino‐acid ring of human C‐type NP (CNP) with the N‐ and the C‐termini of human B‐type NP (BNP). CBB‐NP exerted natriuretic, diuretic, renal‐preserving and cardiac‐unloading actions in anesthetized dogs. In this investigation, we compared for the first time the cGMP stimulating actions of CBB‐NP <jats:italic>vs</jats:italic> human atrial NP (ANP), BNP and CNP in human aortic endothelial cells (HAEC).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>CBB‐NP was synthesized (SPKMVQGSGCFGLKLDRIGSMSGLGCKVLRRH with a disulfide bond joining the C residues). HAEC were incubated with ANP, BNP, CNP or CBB‐NP for 10 min (10<jats:sup>−6</jats:sup> M). Cyclic GMP was quantified by RIA.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>CBB‐NP and CNP increased cGMP (pmol/mL) <jats:italic>vs</jats:italic> control (0.108±0.020 and 0.174±0.036 <jats:italic>vs</jats:italic> 0.001±0.001, P&lt;0.01 and &lt;0.001, respectively). CBB‐NP elicited a greater cGMP response <jats:italic>vs</jats:italic> ANP (0.027±0.002, P&lt;0.05), whereas comparable responses were observed <jats:italic>vs</jats:italic> BNP and CNP. When the native NPs were compared, a greater cGMP stimulating response was detected with CNP <jats:italic>vs</jats:italic> ANP and BNP (P&lt;0.001 and &lt;0.01, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The novel designer NP, CBB‐NP, stimulates cGMP in human aortic endothelial cells to a comparable extent as compared to the native BNP and CNP. Moreover, its cGMP stimulating action is greater than that of ANP. The therapeutic potential of CBB‐NP in models of cardiovascular diseases warrants further investigation.</jats:p><jats:p>Supported by NIH, HFSA and ASCPT</jats:p></jats:sec>