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  1. Article ; Online: A role for pericytes in coronary no-reflow.

    O'Farrell, Fergus M / Attwell, David

    Nature reviews. Cardiology

    2014  Volume 11, Issue 7, Page(s) 427–432

    Abstract: Despite efforts to restore tissue perfusion after myocardial infarction, coronary no-reflow--a failure to achieve adequate reperfusion of the cardiac microcirculation--is a common complication, which correlates with an increased incidence of death and ... ...

    Abstract Despite efforts to restore tissue perfusion after myocardial infarction, coronary no-reflow--a failure to achieve adequate reperfusion of the cardiac microcirculation--is a common complication, which correlates with an increased incidence of death and disability. The treatment of ischaemic stroke is also plagued by no-reflow and, in the brain, a major cause of this phenomenon has been shown to be contractile microvascular pericytes irreversibly constricting capillaries and dying. We propose that cardiac pericytes, which are the second most-common cell type in the heart, impede reperfusion of coronary capillaries in a similar fashion to those in the brain after a stroke. Pericyte constriction might contribute to morbidity in patients by causing microvascular obstruction, even after successful treatment of coronary artery block. The similarity of the no-reflow phenomenon in the brain and in the heart suggests that cardiac pericytes are a novel therapeutic target for coronary no-reflow after myocardial infarction.
    MeSH term(s) Coronary Circulation/physiology ; Humans ; Microcirculation/physiology ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Pericytes/pathology
    Language English
    Publishing date 2014-04-29
    Publishing country England
    Document type Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2490375-9
    ISSN 1759-5010 ; 1759-5002
    ISSN (online) 1759-5010
    ISSN 1759-5002
    DOI 10.1038/nrcardio.2014.58
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: What is a pericyte?

    Attwell, David / Mishra, Anusha / Hall, Catherine N / O'Farrell, Fergus M / Dalkara, Turgay

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2016  Volume 36, Issue 2, Page(s) 451–455

    Abstract: Pericytes, spatially isolated contractile cells on capillaries, have been reported to control cerebral blood flow physiologically, and to limit blood flow after ischaemia by constricting capillaries and then dying. Paradoxically, a recent paper dismisses ...

    Abstract Pericytes, spatially isolated contractile cells on capillaries, have been reported to control cerebral blood flow physiologically, and to limit blood flow after ischaemia by constricting capillaries and then dying. Paradoxically, a recent paper dismisses the idea of pericytes controlling cerebral blood flow, despite confirming earlier data showing a role for pericytes. We show that these discrepancies are apparent rather than real, and depend on the new paper defining pericytes differently from previous reports. An objective definition of different sub-classes of pericyte along the capillary bed is needed to develop novel therapeutic approaches for stroke and disorders caused by pericyte malfunction.
    MeSH term(s) Animals ; Capillaries/cytology ; Capillaries/physiology ; Cerebrovascular Circulation/physiology ; Humans ; Pericytes/physiology ; Pericytes/ultrastructure ; Terminology as Topic
    Language English
    Publishing date 2016-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1177/0271678X15610340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Capillary pericytes mediate coronary no-reflow after myocardial ischaemia.

    O'Farrell, Fergus M / Mastitskaya, Svetlana / Hammond-Haley, Matthew / Freitas, Felipe / Wah, Wen Rui / Attwell, David

    eLife

    2017  Volume 6

    Abstract: After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic ' ...

    Abstract After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.
    MeSH term(s) Animals ; Capillaries/physiopathology ; Coronary Vessels/physiopathology ; Myocardial Ischemia/physiopathology ; Perfusion ; Pericytes/physiology ; Rats
    Language English
    Publishing date 2017-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.29280
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  4. Article ; Online: Capillary pericytes mediate coronary no-reflow after myocardial ischaemia

    Fergus M O'Farrell / Svetlana Mastitskaya / Matthew Hammond-Haley / Felipe Freitas / Wen Rui Wah / David Attwell

    eLife, Vol

    2017  Volume 6

    Abstract: After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic ' ...

    Abstract After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.
    Keywords pericyte ; capillary ; heart ; ischaemia ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Imaging pericytes and capillary diameter in brain slices and isolated retinae.

    Mishra, Anusha / O'Farrell, Fergus M / Reynell, Clare / Hamilton, Nicola B / Hall, Catherine N / Attwell, David

    Nature protocols

    2014  Volume 9, Issue 2, Page(s) 323–336

    Abstract: The cerebral circulation is highly specialized, both structurally and functionally, and it provides a fine-tuned supply of oxygen and nutrients to active regions of the brain. Our understanding of blood flow regulation by cerebral arterioles has evolved ... ...

    Abstract The cerebral circulation is highly specialized, both structurally and functionally, and it provides a fine-tuned supply of oxygen and nutrients to active regions of the brain. Our understanding of blood flow regulation by cerebral arterioles has evolved rapidly. Recent work has opened new avenues in microvascular research; for example, it has been demonstrated that contractile pericytes found on capillary walls induce capillary diameter changes in response to neurotransmitters, suggesting that pericytes could have a role in neurovascular coupling. This concept is at odds with traditional models of brain blood flow regulation, which assume that only arterioles control cerebral blood flow. The investigation of mechanisms underlying neurovascular coupling at the capillary level requires a range of approaches, which involve unique technical challenges. Here we provide detailed protocols for the successful physiological and immunohistochemical study of pericytes and capillaries in brain slices and isolated retinae, allowing investigators to probe the role of capillaries in neurovascular coupling. This protocol can be completed within 6-8 h; however, immunohistochemical experiments may take 3-6 d.
    MeSH term(s) Animals ; Blood-Retinal Barrier/ultrastructure ; Brain/blood supply ; Brain/cytology ; Immunohistochemistry/methods ; Mice ; Microscopy, Fluorescence/methods ; Microscopy, Interference/methods ; Microvessels/ultrastructure ; Models, Biological ; Patch-Clamp Techniques ; Pericytes/ultrastructure
    Language English
    Publishing date 2014-01-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2244966-8
    ISSN 1750-2799 ; 1754-2189
    ISSN (online) 1750-2799
    ISSN 1754-2189
    DOI 10.1038/nprot.2014.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Capillary pericytes regulate cerebral blood flow in health and disease.

    Hall, Catherine N / Reynell, Clare / Gesslein, Bodil / Hamilton, Nicola B / Mishra, Anusha / Sutherland, Brad A / O'Farrell, Fergus M / Buchan, Alastair M / Lauritzen, Martin / Attwell, David

    Nature

    2014  Volume 508, Issue 7494, Page(s) 55–60

    Abstract: Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary ... ...

    Abstract Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.
    MeSH term(s) Animals ; Arterioles/physiology ; Blood-Brain Barrier/pathology ; Blood-Brain Barrier/physiopathology ; Brain Ischemia/pathology ; Capillaries/cytology ; Capillaries/drug effects ; Cell Death ; Cerebellum/blood supply ; Cerebral Cortex/blood supply ; Cerebral Cortex/cytology ; Cerebrovascular Circulation/drug effects ; Cerebrovascular Circulation/physiology ; Dinoprostone/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; Functional Neuroimaging ; Glutamic Acid/pharmacology ; Hydroxyeicosatetraenoic Acids/biosynthesis ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Pericytes/cytology ; Pericytes/drug effects ; Pericytes/pathology ; Pericytes/physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Glutamate/metabolism ; Signal Transduction/drug effects ; Stroke/pathology ; Vasoconstriction ; Vasodilation/drug effects
    Chemical Substances Excitatory Amino Acid Antagonists ; Hydroxyeicosatetraenoic Acids ; Receptors, Glutamate ; Nitric Oxide (31C4KY9ESH) ; Glutamic Acid (3KX376GY7L) ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2014-03-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature13165
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