Deciphering the endothelial shear stress sensor.

The single nonmotile primary cilium, protruding several microns from the apical surface, contains cytoskeletal elements in a specific fashion. It consists of 9 circularly arranged microtubule doublets, as revealed by transmission electron microscopy,1 but lacks the central ones characteristic for motile cilia and flagellae. The primary cilium is anchored to the basal body and is thereby connected to the cytoskeletal apparatus. Sorokin1 concluded that primary cilia were probably vestigial remnants of motile cilia. We now know that ciliary functions are abundant. Examples include processes involving Hedgehog and Wnt signaling2 and determining left–right asymmetry.3 Cilia functioning as sensory antennas in insect ears and the human retina are well established.4 Because of the widespread presence of primary cilia, it does not come as a surprise that many diseases, often syndromic, are caused by ciliary dysfunction. Several diseases are related to disruption of intraflagellar transport in the case of mutation in, for example, Polaris, Kif3a or various Bbs proteins that can lead to such conditions as obesity and Bardet Biedl Syndrome.5 Other cilium-related proteins involve cell membrane–bound calcium channels such as the complex formed by polycystin-1 and -2, encoded from Pkd1 and Pkd2 , respectively. Mutations cause polycystic kidney diseases.6,7 Article p 1161 Primary cilia were first described in the cardiovascular system in human embryos and adults more than 20 years ago.8 The geometry of the heart and vascular tree strongly influences hemodynamics with repercussions on the pattern of ciliation. Endothelial ciliation is restricted to areas of low and oscillatory …

[1]  Heikki Vaananen,et al.  Primary cilia of human endothelial cells disassemble under laminar shear stress , 2004, The Journal of cell biology.

[2]  E. Tzima,et al.  Role of Small GTPases in Endothelial Cytoskeletal Dynamics and the Shear Stress Response , 2006, Circulation research.

[3]  Jing Zhou,et al.  Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells , 2003, Nature Genetics.

[4]  Jing Zhou,et al.  Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. , 2006, Journal of the American Society of Nephrology : JASN.

[5]  Jing Zhou,et al.  Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1 , 2008, Circulation.

[6]  Brian P. Helmke,et al.  The Cytoskeleton Under External Fluid Mechanical Forces: Hemodynamic Forces Acting on the Endothelium , 2002, Annals of Biomedical Engineering.

[7]  A. Antonov,et al.  An ultrastructural study of centriolar complexes in adult and embryonic human aortic endothelial cells. , 1988, Tissue & cell.

[8]  H. Oflaz,et al.  Endothelial dysfunction and increased carotid intima-media thickness in patients with autosomal dominant polycystic kidney disease. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[9]  U. Hopfer,et al.  Force-response considerations in ciliary mechanosensation. , 2007, Biophysical journal.

[10]  Kim Van der Heiden,et al.  Monocilia on chicken embryonic endocardium in low shear stress areas , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[11]  P. Satir,et al.  Overview of structure and function of mammalian cilia. , 2007, Annual review of physiology.

[12]  J. Reiter,et al.  The Primary Cilium as the Cell's Antenna: Signaling at a Sensory Organelle , 2006, Science.

[13]  David A. Schultz,et al.  A mechanosensory complex that mediates the endothelial cell response to fluid shear stress , 2005, Nature.

[14]  A. R. Palmer,et al.  Left-right patterning from the inside out: widespread evidence for intracellular control. , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  Martin Baiker,et al.  Changes in Shear Stress–Related Gene Expression After Experimentally Altered Venous Return in the Chicken Embryo , 2005, Circulation research.

[16]  Kim Van der Heiden,et al.  Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis. , 2008, Atherosclerosis.

[17]  S. Sorokin,et al.  CENTRIOLES AND THE FORMATION OF RUDIMENTARY CILIA BY FIBROBLASTS AND SMOOTH MUSCLE CELLS , 1962, The Journal of cell biology.

[18]  T. Weimbs Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1. , 2007, American journal of physiology. Renal physiology.

[19]  K. Anderson,et al.  Cilia and developmental signaling. , 2007, Annual review of cell and developmental biology.

[20]  Kim Van der Heiden,et al.  Primary cilia sensitize endothelial cells for fluid shear stress , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[21]  B. Hierck,et al.  The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous ligation model. , 2007, Physiology.

[22]  R. Krams,et al.  Effect of shear stress on vascular inflammation and plaque development , 2007, Current opinion in lipidology.