Published online before print June 5, 2003, doi: 10.1161/01.ATV.0000080350.37408.5A
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Vascular Biology |
Increased Mitogenic and Decreased Contractile P2 Receptors in Smooth Muscle Cells by Shear Stress in Human Vessels With Intact Endothelium
From the Department of Cardiology (L.W., D.E.), Lund University Hospital, Lund, Sweden; Clinical Experimental Research Laboratory (M.A., L.K., S.J.), Sahlgrenska University Hospital/Östra, Göteborg University, Göteborg, Sweden; and High Throughput Biology (M.W.) and 7TM Systems Research (D.J.C.), GlaxoSmithKline Research & Development, Stevenage, UK.
Correspondence to David Erlinge, MD, PhD, Department of Cardiology, Lund University Hospital, S-221 85 Lund, Sweden. E-mail david.erlinge{at}kard.lu.se
Objective— We investigated the role of shear stress in regulating P2 receptors in human umbilical vein.
Methods and Results— Using a novel, computerized, biomechanical perfusion model, parallel vessel segments were randomized to simultaneous perfusion under high (25 dyn/cm2) or low (<4 dyn/cm2) shear stress at identical mean perfusion pressure (20 mm Hg) for 6 hours. In the endothelium, no significant P2 receptor mRNA differences were found. In smooth muscle cells (SMCs), high shear stress decreased P2X1 receptors, whereas P2Y2 and P2Y6 receptors were upregulated. These findings were consistent at the mRNA level (real-time reverse transcription–polymerase chain reaction), protein level (Western blot), and morphologically (immunohistochemistry). The changes were more pronounced in the subintimal layer of the media.
Conclusions— Our findings suggest that shear stress might regulate gene expression in SMCs more than in the endothelium in intact vessels. Decreased expression of the contractile P2X1 receptor could lead to reduced vascular tonus and increased blood flow. Because P2Y2 and P2Y6 receptors stimulate growth and migration of SMCs, increased expression of these receptors could promote vascular remodeling induced by shear stress. The pattern of upregulation of mitogenic P2Y receptors and downregulation of contractile P2X1 receptor is similar to changes seen in the phenotypic shift from contractile to synthetic SMCs.
Key Words: smooth muscle cells • shear stress • purinoceptors • gene expression • vascular remodeling
This article has been cited by other articles:
 |
|
 |
|
  M. L. Graciano, A. Nishiyama, K. Jackson, D. M. Seth, R. M. Ortiz, M. C. Prieto-Carrasquero, H. Kobori, and L. G. Navar Purinergic receptors contribute to early mesangial cell transformation and renal vessel hypertrophy during angiotensin II-induced hypertension Am J Physiol Renal Physiol, January 1, 2008; 294(1): F161 - F169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev., March 1, 2006; 58(1): 58 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Vial and R. J. Evans Disruption of Lipid Rafts Inhibits P2X1 Receptor-mediated Currents and Arterial Vasoconstriction J. Biol. Chem., September 2, 2005; 280(35): 30705 - 30711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wang, G. Olivecrona, M. Gotberg, M. L. Olsson, M. S. Winzell, and D. Erlinge ADP Acting on P2Y13 Receptors Is a Negative Feedback Pathway for ATP Release From Human Red Blood Cells Circ. Res., February 4, 2005; 96(2): 189 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Erlinge Extracellular ATP: a central player in the regulation of vascular smooth muscle phenotype. Focus on "Dual role of PKA in phenotype modulation of vascular smooth muscle cells by extracellular ATP" Am J Physiol Cell Physiol, August 1, 2004; 287(2): C260 - C262. [Full Text] [PDF]
|
|