728 x 90

Capillary-selective vasodilation through myosin inhibition halts ischaemic cascades – Nature

Capillary-selective vasodilation through myosin inhibition halts ischaemic cascades – Nature

Freitas, F. & Attwell, D. Pericyte-mediated constriction of renal capillaries evokes no-reflow and kidney injury following ischaemia. eLife 11, e74211 (2022). Article  CAS  PubMed  PubMed Central  Google Scholar  O’Farrell, F. M. & Attwell, D. A role for pericytes in coronary no-reflow. Nat. Rev. Cardiol. 11, 427–432 (2014). Article  PubMed  Google Scholar  Rezkalla, S. H. &

  • Freitas, F. & Attwell, D. Pericyte-mediated constriction of renal capillaries evokes no-reflow and kidney injury following ischaemia. eLife 11, e74211 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • O’Farrell, F. M. & Attwell, D. A role for pericytes in coronary no-reflow. Nat. Rev. Cardiol. 11, 427–432 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Rezkalla, S. H. & Kloner, R. A. No-reflow phenomenon. Circulation 105, 656–662 (2002).

    Article 
    PubMed 

    Google Scholar 

  • O’Farrell, F. M. et al. Capillary pericytes mediate coronary no-reflow after myocardial ischaemia. eLife 6, e29280 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pénzes, M. et al. Direct myosin-2 inhibition enhances cerebral perfusion resulting in functional improvement after ischemic stroke. Theranostics 10, 5341–5356 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kloner, R. A., Ganote, C. E. & Jennings, R. B. The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J. Clin. Invest. 54, 1496–1508 (1974).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lameire, N. H. et al. Acute kidney injury: an increasing global concern. Lancet 382, 170–179 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Mehta, R. L. et al. International Society of Nephrology’s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet 385, 2616–2643 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Gibson, C. M. et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 101, 125–130 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ndrepepa, G. et al. Coronary no-reflow and adverse events in patients with acute myocardial infarction after percutaneous coronary intervention with current drug-eluting stents and third-generation P2Y12 inhibitors. Clin. Res. Cardiol. 113, 1006–1016 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zhang, B. et al. The coronary angiography-derived index of microcirculatory resistance predicts perioperative myocardial injury in stable coronary artery disease patients undergoing PCI. Heliyon 10, e35240 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nicolau, A. M. et al. Molecular mechanisms of microvascular obstruction and dysfunction in percutaneous coronary interventions: from pathophysiology to therapeutics—a comprehensive review. Int. J. Mol. Sci. 26, 6835 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Peppiatt, C. M., Howarth, C., Mobbs, P. & Attwell, D. Bidirectional control of CNS capillary diameter by pericytes. Nature 443, 700–704 (2006).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yemisci, M. et al. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat. Med. 15, 1031–1037 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Berthiaume, A.-A., Hartmann, D. A., Majesky, M. W., Bhat, N. R. & Shih, A. Y. Pericyte structural remodeling in cerebrovascular health and homeostasis. Front. Aging Neurosci. 10, 210 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Erdener, ŞE., Küreli, G. & Dalkara, T. Contractile apparatus in CNS capillary pericytes. Neurophotonics 9, 021904 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Le, D. E., Zhao, Y. & Kaul, S. Persistent coronary vasomotor tone during myocardial ischemia occurs at the capillary level and may involve pericytes. Front. Cardiovasc. Med. 9, 930492 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fu, J., Liang, H., Yuan, P., Wei, Z. & Zhong, P. Brain pericyte biology: from physiopathological mechanisms to potential therapeutic applications in ischemic stroke. Front. Cell. Neurosci. 17, 1267785 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fraser, J. F. et al. Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective in stroke. J. Cereb. Blood Flow Metab. 37, 3531–3543 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nazir, S. A. et al. The REFLO-STEMI (REperfusion Facilitated by LOcal adjunctive therapy in ST-Elevation Myocardial Infarction) trial: a randomised controlled trial comparing intracoronary administration of adenosine or sodium nitroprusside with control for attenuation of microvascular obstruction during primary percutaneous coronary intervention. Efficacy Mech. Eval. https://doi.org/10.3310/eme03090 (2016).

  • Hill, R. A. et al. Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes. Neuron 87, 95–110 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hall, C. N. et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508, 55–60 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rangaswami, J. et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the american heart association. Circulation 139, e840–e878 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Mancianti, N., Calatroni, M., Deferrari, G. & La Porta, E. Editorial: kidney and heart cross-talk. Front. Nephrol. 5, 1598135 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • McCullough, P. A. & Ronco, C. Heart-Kidney Cross-Talk. in Critical Care Nephrology Ch. 109, 664–670.e3 https://doi.org/10.1016/B978-0-323-44942-7.00109-6 (Elsevier, 2019).

  • House, A. A. et al. Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int. 95, 1304–1317 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Ronco, C., Bellomo, R. & Kellum, J. A. Acute kidney injury. Lancet 394, 1949–1964 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Annibali, G. et al. “No-reflow” phenomenon: a contemporary review. J. Clin. Med. 11, 2233 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wanjare, M., Kusuma, S. & Gerecht, S. Perivascular cells in blood vessel regeneration. Biotechnol. J. 8, 434–447 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Suthar, S. K. et al. Comprehensive SAR analysis of actomyolytics, drug candidates targeting the actomyosin complex. Eur. J. Med. Chem. 299, 117999 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gyimesi, M. et al. Single residue variation in skeletal muscle myosin enables direct and selective drug targeting for spasticity and muscle stiffness. Cell 183, 335–346.e13 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Straight, A. F. et al. Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor. Science 299, 1743–1747 (2003).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Allingham, J. S., Smith, R. & Rayment, I. The structural basis of blebbistatin inhibition and specificity for myosin II. Nat. Struct. Mol. Biol. 12, 378–379 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sirigu, S. et al. Highly selective inhibition of myosin motors provides the basis of potential therapeutic application. Proc. Natl Acad. Sci. USA 113, E7448–E7455 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Haase, M. et al. Pathogenesis of cardiorenal syndrome type 1 in acute decompensated heart failure: workgroup statements from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib. Nephrol. 182, 99–116 (2013).

    Article 
    PubMed 

    Google Scholar 

  • Virzì, G. M. et al. The hemodynamic and nonhemodynamic crosstalk in cardiorenal syndrome type 1. Cardiorenal Med. 4, 103–112 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Divakaran, S. & Loscalzo, J. The role of nitroglycerin and other nitrogen oxides in cardiovascular therapeutics. J. Am. Coll. Cardiol. 70, 2393–2410 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Aetesam-ur-Rahman, M. et al. Adenosine-induced coronary steal is observed in patients presenting with ST-segment–elevation myocardial infarction. J. Am. Heart Assoc. 10, e019899 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Juricic, S. et al. Molecular and cellular mechanisms of myocardial ischemia and reperfusion injury: a narrative review. Cells 15, 265 (2026).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Steegh, F. M. E. G. et al. Early loss of peritubular capillaries after kidney transplantation. J. Am. Soc. Nephrol. 22, 1024–1029 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ajtai, K., Mayanglambam, A., Wang, Y. & Burghardt, T. P. Human tonic and phasic smooth muscle myosin isoforms are unresponsive to the loop 1 insert. ISRN Struct. Biol. 2013, 634341 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gyimesi, M. et al. The mechanism of the reverse recovery step, phosphate release, and actin activation of Dictyostelium myosin II. J. Biol. Chem. 283, 8153–8163 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Vonrhein, C. et al. Data processing and analysis with the autoPROC toolbox. Acta Crystallogr. D Biol. Crystallogr. 67, 293–302 (2011).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296–W303 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

    Article 
    ADS 
    PubMed 

    Google Scholar 

  • Bricogne G. et al. BUSTER v.2.10.3. https://sbgrid.org/software/titles/buster (Global Phasing, 2018).

  • Mulvany, M. J. & Halpern, W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ. Res. 41, 19–26 (1977).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mastitskaya, S., de Freitas, F. S. S., Evans, L. E. & Attwell, D. GLP-1 activates KATP channels in coronary pericytes as the effector of brain-gut-heart signalling mediating cardioprotection. Nat. Commun. 17, 2773 (2026).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Besseling, P. J. et al. A plasma creatinine- and urea-based equation to estimate glomerular filtration rate in rats. Am. J. Physiol. Renal Physiol. 320, F518–F524 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Seylaz, J. et al. Dynamic in vivo measurement of erythrocyte velocity and flow in capillaries and of microvessel diameter in the rat brain by confocal laser microscopy. J. Cereb. Blood Flow Metab. 19, 863–870 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liebschner, D. et al. Polder maps: improving OMIT maps by excluding bulk solvent. Acta Crystallogr. Struct. Biol. 73, 148–157 (2017).

    Article 
    ADS 
    CAS 

    Google Scholar 

  • For more tech updates, stay tuned to our blog.

    Posts Carousel

    Latest Posts

    Top Authors

    Most Commented

    Featured Videos