Decreased thromboembolic stroke but not atherosclerosis or vascular remodelling in mice with ROCK2-deficient platelets

Cardiovascular Research

Volumn 113, Issue 11, 2017, Pages 1307-1317

  Sladojevic, Nikola ^a   Taeg Oh, Goo ^b,c   Kim, Hyung Hwan ^b   Beaulieu, Lea M ^d   Falet, Hervé ^b   Kamiński, Karol ^b,e   Freedman, Jane E ^d   Liao, James K ^a,b  

^a Pritzker School of Medicine   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c Ewha Womans University   (South Korea)

^d UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^e MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

Author keywords

Atherosclerosis; Platelet; Rho kinase; Stroke; Thrombosis

Indexed keywords

GLYCOPROTEIN; PADGEM PROTEIN; RHO ASSOCIATED COILED COIL CONTAINING KINASE 2; RHO KINASE; THROMBIN; THROMBOCYTE FACTOR 4; UNCLASSIFIED DRUG; ROCK2 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATHEROGENIC DIET; ATHEROSCLEROSIS; BLEEDING TIME; BLOOD CLOTTING; BLOOD FLOW; BLOOD VESSEL OCCLUSION; BRAIN BLOOD FLOW; BRAIN INJURY; CEREBROVASCULAR ACCIDENT; COLLAGEN SYNTHESIS; COMMON CAROTID ARTERY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; HEMOSTASIS; ISCHEMIC STROKE; MALE; MIDDLE CEREBRAL ARTERY; MOUSE; NEUROLOGICAL DEFICIT SCORE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PSEUDOPODIUM; THROMBOCYTE; THROMBOCYTE ADHESION; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOCYTE MEMBRANE; THROMBOEMBOLISM; THROMBOSIS; VASCULAR REMODELING; ANIMAL; C57BL MOUSE; DEFICIENCY; DISEASE MODEL; GENETICS; METABOLISM; PATHOLOGY; THROMBOCYTE ACTIVATION; TRANSGENIC MOUSE;

ANIMALS; ATHEROSCLEROSIS; BLOOD PLATELETS; DISEASE MODELS, ANIMAL; MICE, INBRED C57BL; MICE, TRANSGENIC; PLATELET ACTIVATION; PLATELET AGGREGATION; RHO-ASSOCIATED KINASES; STROKE; THROMBIN; THROMBOSIS; VASCULAR REMODELING;

EID: 85048298808     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvx071     Document Type: Article

References (34)

1. del Zoppo GJ. The role of platelets in ischemic stroke. Neurology 1998; 51:S9-S14.
2. Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 2008; 112:3555-3562.
3. Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 2003; 4:399-415.
4. Riento K, Ridley AJ. Rocks: Multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003; 4:446-456.
5. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 1999; 285:895-898.
6. Carroll RC, Butler RG, Morris PA, Gerrard JM. Separable assembly of platelet pseudopodal and contractile cytoskeletons. Cell 1982; 30:385-393.
7. Wang LL, Bryan J. Isolation of calcium-dependent platelet proteins that interact with actin. Cell 1981; 25:637-649.
8. Noma K, Rikitake Y, Oyama N, Yan G, Alcaide P, Liu PY, Wang H, Ahl D, Sawada N, Okamoto R, Hiroi Y, Shimizu K, Luscinskas FW, Sun J, Liao JK. ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. J Clin Invest 2008; 118:1632-1644.
9. Shimizu Y, Thumkeo D, Keel J, Ishizaki T, Oshima H, Oshima M, Noda Y, Matsumura F, Taketo MM, Narumiya S. ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol 2005; 168:941-953.
10. Thumkeo D, Keel J, Ishizaki T, Hirose M, Nonomura K, Oshima H, Oshima M, Taketo MM, Narumiya S. Targeted disruption of the mouse rho-associated kinase 2 gene results in intrauterine growth retardation and fetal death. Mol Cell Biol 2003; 23:5043-5055.
11. Aslan JE, McCarty OJ. Rho GTPases in platelet function. J Thromb Haemost 2013; 11:35-46.
12. McCarty OJ, Larson MK, Auger JM, Kalia N, Atkinson BT, Pearce AC, Ruf S, Henderson RB, Tybulewicz VL, Machesky LM, Watson SP. Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow. J Biol Chem2005; 280:39474-39484.
13. Pleines I, Eckly A, Elvers M, Hagedorn I, Eliautou S, Bender M, Wu X, Lanza F, Gachet C, Brakebusch C, Nieswandt B. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood 2010; 115:3364-3373.
14. Pleines I, Hagedorn I, Gupta S, May F, Chakarova L, van Hengel J, Offermanns S, Krohne G, Kleinschnitz C, Brakebusch C, Nieswandt B. Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis. Blood 2012; 119:1054-1063.
15. Masumoto A, Mohri M, Shimokawa H, Urakami L, Usui M, Takeshita A. Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation 2002; 105:1545-1547.
16. Sato M, Tani E, Fujikawa H, Kaibuchi K. Involvement of Rho-kinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res 2000; 87:195-200.
17. Masumoto A, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension 2001; 38:1307-1310.
18. Kataoka C, Egashira K, Inoue S, Takemoto M, Ni W, Koyanagi M, Kitamoto S, Usui M, Kaibuchi K, Shimokawa H, Takeshita A. Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 2002; 39:245-250.
19. Sawada N, Itoh H, Ueyama K, Yamashita J, Doi K, Chun TH, Inoue M, Masatsugu K, Saito T, Fukunaga Y, Sakaguchi S, Arai H, Ohno N, Komeda M, Nakao K. Inhibition of rho-associated kinase results in suppression of neointimal formation of ballooninjured arteries. Circulation 2000; 101:2030-2033.
20. Mallat Z, Gojova A, Sauzeau V, Brun V, Silvestre JS, Esposito B, Merval R, Groux H, Loirand G, Tedgui A. Rho-associated protein kinase contributes to early atherosclerotic lesion formation in mice. Circ Res 2003; 93:884-888.
21. Feske SK, Sorond FA, Henderson GV, Seto M, Hitomi A, Kawasaki K, Sasaki Y, Asano T, Liao JK. Increased leukocyte ROCK activity in patients after acute ischemic stroke. Brain Res 2009; 1257:89-93.
22. Kajikawa M, Noma K, Maruhashi T, Mikami S, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Liao JK, Higashi Y. Rho-associated kinase activity is a predictor of cardiovascular outcomes. Hypertension 2014; 63:856-864.
23. Dong M, Jiang X, Liao JK, Yan BP. Elevated rho-kinase activity as a marker indicating atherosclerosis and inflammation burden in polyvascular disease patients with concomitant coronary and peripheral arterial disease. Clin Cardiol 2013; 36:347-351.
24. Okamoto R, Li Y, Noma K, Hiroi Y, Liu PY, Taniguchi M, Ito M, Liao JK. FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2. FASEB J 2013; 27:1439-1449.
25. Tiedt R, Schomber T, Hao-Shen H, Skoda RC. Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo. Blood 2007; 109:1503-1506.
26. Rikitake Y, Kim HH, Huang Z, Seto M, Yano K, Asano T, Moskowitz MA, Liao JK. Inhibition of Rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection. Stroke 2005; 36:2251-2257.
27. Zhang Z, Chopp M, Zhang RL, Goussev A. A mouse model of embolic focal cerebral ischemia. J Cereb Blood Flow Metab 1997; 17:1081-1088.
28. Suzuki A, Shin JW, Wang Y, Min SH, Poncz M, Choi JK, Discher DE, Carpenter CL, Lian L, Zhao L, Wang Y, Abrams CS. RhoA is essential for maintaining normal megakaryocyte ploidy and platelet generation. PLoS One 2013; 8:e69315.
29. Chang Y, Aurade F, Larbret F, Zhang Y, Le Couedic JP, Momeux L, Larghero J, Bertoglio J, Louache F, Cramer E, Vainchenker W, Debili N. Proplatelet formation is regulated by the Rho/ROCK pathway. Blood 2007; 109:4229-4236.
30. Moers A, Nieswandt B, Massberg S, Wettschureck N, Gruner S, Konrad I, Schulte V, Aktas B, Gratacap MP, Simon MI, Gawaz M, Offermanns S. G13 is an essential mediator of platelet activation in hemostasis and thrombosis. Nat Med 2003; 9:1418-1422.
31. Woronowicz K, Dilks JR, Rozenvayn N, Dowal L, Blair PS, Peters CG, Woronowicz L, Flaumenhaft R. The platelet actin cytoskeleton associates with SNAREs and participates in alpha-granule secretion. Biochemistry 2010; 49:4533-4542.
32. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357:2482-2494.
33. Ross R, Glomset JA. The pathogenesis of atherosclerosis (first of two parts). N Engl J Med 1976; 295:369-377.
34. Zhou Q, Mei Y, Shoji T, Han X, Kaminski K, Oh GT, Ongusaha PP, Zhang K, Schmitt H, Moser M, Bode C, Liao JK. Rho-associated coiled-coil-containing kinase 2 deficiency in bone marrow-derived cells leads to increased cholesterol efflux and decreased atherosclerosis. Circulation 2012; 126:2236-2247