Eur J Vasc Endovasc Surg (2011) 41, 597e598
Manipulating Arterial Fluid-shear Stress and Arteriogenesis in the Brain P.-H. Rolland*, L. Bruzzese Dept. of Physiopathology and Vascular Therapeutics, La Timone School of Medicine, 27 Bld. Jean-Moulin, 13385 Marseille Cedex 5, France Submitted 16 February 2011; accepted 17 February 2011 Available online 8 March 2011 Occlusions of the brain arteries remain life-threatening diseases and are associated with devastating morbidity. The basic, physiological and spontaneous reactions of the organism to vascular occlusion are to develop adaptative collateral circulation(s) outside the ischemic region, which can potentially replace the feeding capacity of the larger arteries. From the point of view of the interventionalist, the intracranial anatomy, as well as the extreme mechanosensitivity of the brain arteries, leave few degrees of freedom to surgical actions, in contrast to situations elsewhere in the body. Moreover there are major differences between the brain arteries and their constitutive vascular cells of the brain with arteries lying outside the brain. The cerebral vasculature is made of low-resistance vessels containing neural crest-derived vascular cells opposing high-resistance vessels made of mesoderm-derived vascular smooth muscle cells in the peripheral arteries. The paper by Wilma Schierling and colleagues1 is one example of the recent attempts to develop new therapeutic options aimed at favoring the brain arteriogenesis by acting upon the haemodynamic properties of cerebral arteries by modifying one of the blood flow components, i.e. the fluid-shear stress which previously has been shown to be the pivotal trigger of cerebral arteriogenesis.2e4 Various experimental models have been used.1e4 The present experimental model is based upon double ligature, * Corresponding author. Tel.: þ33 4 9132 4230; fax: þ33 4 9132 4396. E-mail address: [email protected]
AV shunts compared with sham procedures of the carotid arteries, and follow-up is based on imaging and appropriate molecular and haemodynamic investigations in the posterior cerebral arteries after 7 days. There is abundant literature, which addresses the molecular machinery of neoangiogenesis and arteriogenesis, focusing on a large variety of vascular cell growth factors. The present paper is part of a programme by the same team to investigate whether calcium-dependent signalling potentially plays and important role in neovascularization and arteriogenesis, whether or not associated with ischaemic processes.3,4 The authors attempt to establish relationships between maximally-induced shear stress and the activation of vascular mechano-receptors; specifically, the transient receptor potential cation channels (trp), as compared with trp activation by drugs (e.g. phorbol ester and ruthenium red, which are not available for human use). The major finding of the present report is the identification of the 4th member of the subfamily V of the mechanosensitive transient receptor potential cationchannel (Trpv4) as the pivotal fluid-shear stress-sensitive actor of arteriogenesis. The pharmacological activation of Trpv4 increases both m-RNA and protein-expression in brain vessels and increased collateral growth to the same extent as did maximum fluidshear stress-stimulation. Although the present study raised numerous questions, such as the identification of functional and downstream consequences of the procedures there are basic innovative findings. The study offers a prospect of a novel molecular target for new therapeutic strategies. In addition, the modality of altering brain hemodynamics in order to
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598 activate cerebral arteriogenesis is highlighted. Of high potential interest is the finding that preventing rapid normalization of fluidshear stress (as exampled using AV shunts) furthers arteriogenesis in a non-pharmacological manner. These promising early results require assessment of whether they can be translated into the clinical situation of how to utilize either or both molecular and haemodynamics therapeutic targets.
References 1 Schierling W, Troidl H, Apfelbeck H, Troidl C, Kasprzak PM, Schaper W, Schmitz-Rixen T. Cerebral arteriogenesis is enhanced
P.-H. Rolland, L. Bruzzese by pharmacological as well as fluid-shear-stress activation of the Trpv4 calcium channel. Eur J Vasc Endovasc Surg 2011;41: 589e96. 2 Pipp F, Boehm S, Cai WJ, Adili F, Ziegler B, Karanovic G, et al. Elevated fluid shear stress enhances postocclusive collateral artery growth and gene expression in the pig hind limb. Arterioscler Thromb Vasc Biol 2004;24:1664e8. 3 Schierling W, Troidl K, Mueller C, Troidl C, Wustrack H, Bachmann G, et al. Increased intravascular flow rate triggers cerebral arteriogenesis. J Cereb Blood Flow Metab 2009;29: 726e37. 4 Troidl K, Ruding I, Cai WJ, Mucke Y, Grossekettler L, Piotrowska I, et al. Actin-binding Rho activating protein (ABRA) is essential for fluid shear stress-induced arteriogenesis. Arterioscler Thromb Vasc Biol 2009;29:2093e101.