Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis

Heiden, Kim Van der; Hierck, Beerend P.; Krams, Rob; Crom, Rini de; Cheng, Caroline; Baiker, Martin; Pourquié, Mathieu; Alkemade, Fanneke E.; DeRuiter, Marco C.; Groot, Adriana C. Gittenberger‐de; Poelmann, Robert E.

doi:10.1016/j.atherosclerosis.2007.05.030

Cited by 151 publications

(137 citation statements)

References 37 publications

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“…These structures are well known to sense fluid flow by bending (Van der Heiden et al, 2011). Primary cilia are disrupted by high shear in vitro (Iomini et al, 2004) and absent in most regions of arteries (Van der Heiden et al, 2006;Van der Heiden et al, 2008), which makes it unlikely that they are required for transducing the anti-atherosclerotic effects of high laminar shear. However, they are detectable in a fraction of the ECs in regions of low and disturbed flow (Van der Heiden et al, 2006;Van der Heiden et al, 2008): precisely the regions that are susceptible to atherosclerosis.…”

Section: Mechanosensors Of Endothelial Shear Stressmentioning

confidence: 99%

Flow-dependent cellular mechanotransduction in atherosclerosis

Conway

Schwartz

2013

Journal of Cell Science

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SummaryAtherosclerosis depends on risk factors such as hyperlipidemia, smoking, hypertension and diabetes. Although these risk factors are relatively constant throughout the arterial circulation, atherosclerotic plaques occur at specific sites where flow patterns are disturbed, with lower overall magnitude and complex changes in speed and direction. Research over the past few decades has provided new insights into the cellular mechanisms of force transduction and how mechanical effects act in concert with conventional risk factors to mediate plaque formation and progression. This Commentary summarizes our current understanding of how mechanotransduction pathways synergize with conventional risk factors in atherosclerosis. We attempt to integrate cellular studies with animal and clinical data, and highlight major questions that need to be answered to develop more effective therapies.

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Section: Mechanosensors Of Endothelial Shear Stressmentioning

confidence: 99%

Flow-dependent cellular mechanotransduction in atherosclerosis

Conway

Schwartz

2013

Journal of Cell Science

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“…Polycystin-2 (PKD2 gene), a calcium channel which acts in cilia together with the mechanosensory protein polycystin-1 (PKD1 gene), also contributes significantly to these inward calcium currents (5,1287,1814). While most arterial endothelial cells are not ciliated, cilia are found frequently in atherosclerosis-prone areas, and their formation may be induced by disturbed flow (1847). ATP is released to the extracellular space by endothelial cells in response to flow followed by autocrine stimulation of the purinergic P2X 4 calcium channel (encoded by the P2RX4 gene).…”

Section: Calcium Signaling Ion Channels and Weibel-palade Body Exocmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…Recently, monocilia on endothelial cells in chick embryos and primary cilia on human vascular endothelial cells have been found in regions exposed to low or oscillatory shear stress. These have been proposed to contribute to endothelial activation and dysfunction (Van der Heiden, Groenendijk et al 2006;Van der Heiden, Hierck et al 2008). Caveolae have also been suggested to act as mechanoreceptors.…”

Section: Importance Of Flowmentioning

confidence: 99%

ICAM-1: Contribution to Vascular Inflammation and Early Atherosclerosis

Wolf¹

2012

Coronary Artery Disease - New Insights and Novel Approaches

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Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis

Cited by 151 publications

References 37 publications

Flow-dependent cellular mechanotransduction in atherosclerosis

Flow-dependent cellular mechanotransduction in atherosclerosis

Molecular Biology of Atherosclerosis

ICAM-1: Contribution to Vascular Inflammation and Early Atherosclerosis

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