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Shear Stress Induction of C-type Natriuretic Peptide (CNP) in Endothelial Cells is Independent of NO Autocrine Signaling

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Abstract

C-type natriuretic peptide (CNP) is secreted by endothelial cells and has vasodilatory and antiproliferative activity against smooth muscle cells. Using defined laminar shear stress exposures of cultured bovine aortic endothelial cells, we investigated the regulation of CNP gene by PhosphorImaging the ratio of CNP mRNA to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. A 6 h exposure to arterial shear stress of 25 dyn/cm2 caused a marked elevation (10.5 ± 6.2-fold; n=10, p < 0.001) of CNP/GAPDH mRNA ratio compared to stationary controls. Arterial shear stress was 2.6 times more potent than a venous level of shear stress of 4 dyn/cm2 in elevating the CNP/GAPDH mRNA ratio. After 6 h, CNP secretion by shear stressed BAEC was elevated over stationary controls by 3.1-fold (n=5, p < 0.001) to a level of 34 ± 7.5pg/cm2 BAEC. Shear stress elevated CNP mRNA in the presence of L-NAME (400 μM) indicating that autocrine signaling through shear-induced NO production or guanylate cyclase activation was not involved. Similarly, the tyrosine kinase inhibitor genistein (10 μM), which can also block shear-induced NO production, had no effect on CNP mRNA induction by shear stress in BAEC. The intracellular calcium chelator BAPTA/AM (5 μM) attenuated the shear stress-induced CNP mRNA expression by 71%. Interestingly, dexamethasone (1 μM) potentiated by 2-fold the shear stress enhancement of CNP mRNA. Shear stress was a more potent inducer of CNP than either phorbol myristrate acetate or lipopolysaccharide. Hemodynamic shear stress may be an important physiological regulator of CNP expression with consequent effects on vasodilation and regulation of intimal hyperplasia. © 1999 Biomedical Engineering Society.

PAC99: 8717-d, 8719Tt

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Authors and Affiliations

  1. Bioengineering Laboratory, Department of Chemical Engineering, The State University of New York at Buffalo, Buffalo, NY

    Zhaohui Zhang & Zeshuai Xiao

  2. Institute for Medicine and Engineering, Department of Chemical Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA

    Scott L. Diamond

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Zhang, Z., Xiao, Z. & Diamond, S.L. Shear Stress Induction of C-type Natriuretic Peptide (CNP) in Endothelial Cells is Independent of NO Autocrine Signaling. Annals of Biomedical Engineering 27, 419–426 (1999). https://doi.org/10.1114/1.203

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