Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

Patrick Horn, Theodor Baars, Philipp Kahlert, Christian Heiss, Ralf Westenfeld, Malte Kelm, Raimund Erbel, Gerd Heusch, Petra Kleinbongard, Patrick Horn, Theodor Baars, Philipp Kahlert, Christian Heiss, Ralf Westenfeld, Malte Kelm, Raimund Erbel, Gerd Heusch, Petra Kleinbongard

Abstract

Objective: Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs.

Methods: In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41+, endothelium-derived MPs (EMPs) as CD144+, CD62E+ and CD31+/CD41-, leukocyte-derived MPs as CD45+, and erythrocyte-derived MPs as CD235+.

Results: In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41+: 2729.6 ± 645.6 vs. 4208.7 ± 679.4 and 2355.9 ± 503.9 vs. 3285.8 ± 733.2 nr/µL; CD144+: 451.5 ± 87.9 vs. 861.7 ± 147.0 and 444.6 ± 74.8 vs. 726.5 ± 136.4 nr/µL; CD62E+: 1404.1 ± 247.7 vs. 1844.3 ± 378.6 and 1084.6 ± 211.0 vs. 1783.8 ± 384.3 nr/µL, P < 0.05), but not different between RCAs and SVG-RCAs.

Conclusion: Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs.

Trial registration: ClinicalTrials.gov NCT01430884.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. RCA and SVG-RCA plaque volume…
Fig 1. RCA and SVG-RCA plaque volume (A) and composition (B) by IVUS VH analysis.
Data are mean±SEM, comparison by unpaired t-test. RCA = native right coronary arteries, SVG-RCA = saphenous vein grafts on right coronary arteries.
Fig 2. Plasma concentration of TF, and…
Fig 2. Plasma concentration of TF, and number of TF-bearing MPs in RCA and SVG-RCA before and after stent implantation.
Data are presented as minimum and maximum (crosses), interquartile range from 25 to 75% (box), mean (square), and median (line) in a box plot. Comparison between arterial plasma and aspirate plasma as well as RCA and SVG-RCA was done by 2-way repeated measures ANOVA followed by Fishers LSD post-hoc test; MPs = microparticles, nr = number, RCA = native right coronary arteries, SVG-RCA = saphenous vein grafts on right coronary arteries, TF = tissue factor.
Fig 3. Numbers of MPs in RCA…
Fig 3. Numbers of MPs in RCA and SVG-RCA before and after stent implantation.
Numbers of PMPs (CD41+), EMPs (CD144+, CD62E+ or CD31+/CD41-), LMPs (CD45+), and ERMPs (CD235+) are presented as minimum and maximum (crosses), interquartile range from 25 to 75% (box), mean (square), and median (line) in a box plot. Comparison between arterial plasma and aspirate plasma as well as RCA and SVG-RCA was done by 2-way repeated measures ANOVA followed by Fishers LSD post-hoc test; EMPs = endothelium-derived MPs, ERMPs = erythrocyte-derived MPs, LMPs = leukocyte-derived MPs, MPs = microparticles, nr = number, PMPs = platelet-derived MPs, RCA = native right coronary arteries, SVG-RCA = saphenous vein grafts on right coronary arteries.

References

    1. Baars T, Kleinbongard P, Boese D, Konorza T, Moehlenkamp S, Hippler J, et al. Saphenous vein aorto-coronary graft atherosclerosis in patients with chronic kidney disease: more plaque calcification and necrosis, but less vasoconstrictor potential. Basic Res Cardiol. 2012;107: 303 10.1007/s00395-012-0303-3
    1. Leineweber K, Boese D, Vogelsang M, Haude M, Erbel R, Heusch G. Intense vasoconstriction in response to aspirate from stented saphenous vein aortocoronary bypass grafts. J Am Coll Cardiol. 2006;47: 981–986.
    1. Kleinbongard P, Baars T, Mohlenkamp S, Kahlert P, Erbel R, Heusch G. Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris. Am J Physiol Heart Circ Physiol. 2013;305: H1222–H1229. 10.1152/ajpheart.00358.2013
    1. Kleinbongard P, Boese D, Baars T, Moehlenkamp S, Konorza T, Schoener S, et al. Vasoconstrictor potential of coronary aspirate from patients undergoing stenting of saphenous vein aortocoronary bypass grafts and its pharmacological attenuation. Circ Res. 2011;108: 344–352. 10.1161/CIRCRESAHA.110.235713
    1. Heusch G, Kleinbongard P, Boese D, Levkau B, Haude M, Schulz R, et al. Coronary microembolization: from bedside to bench and back to bedside. Circulation. 2009;120: 1822–1836. 10.1161/CIRCULATIONAHA.109.888784
    1. Kleinbongard P, Konorza T, Boese D, Baars T, Haude M, Erbel R, et al. Lessons from human coronary aspirate. J Mol Cell Cardiol. 2012;52: 890–896. 10.1016/j.yjmcc.2011.06.022
    1. Heusch G, Kleinbongard P, Skyschally A. Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship. Basic Res Cardiol. 2013;108: 380 10.1007/s00395-013-0380-y
    1. Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation. 1998;97: 916–931.
    1. Pregowski J, Tyczynski P, Mintz GS, Kim SW, Witkowski A, Waksman R, et al. Incidence and clinical correlates of ruptured plaques in saphenous vein grafts. An intravascular ultrasound study. J Am Coll Cardiol. 2005;45: 1974–1979.
    1. Shantsila E, Kamphuisen PW, Lip GY. Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis. J Thromb Haemost. 2010;8: 2358–2368. 10.1111/j.1538-7836.2010.04007.x
    1. Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res. 2010;107: 1047–1057. 10.1161/CIRCRESAHA.110.226456
    1. Rautou PE, Vion AC, Amabile N, Chironi G, Simon A, Tedgui A, et al. Microparticles, vascular function, and atherothrombosis. Circ Res. 2011;109: 593–606. 10.1161/CIRCRESAHA.110.233163
    1. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol. 2001;3: 339–345.
    1. Horstman LL, Ahn YS. Platelet microparticles: a wide-angle perspective. Crit Rev Oncol Hematol. 1999;30: 111–142.
    1. Jimenez JJ, Jy W, Mauro LM, Soderland C, Horstman LL, Ahn YS. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res. 2003;109: 175–180.
    1. Vion AC, Ramkhelawon B, Loyer X, Chironi G, Devue C, Loirand G, et al. Shear stress regulates endothelial microparticle release. Circ Res. 2013;112: 1323–1333. 10.1161/CIRCRESAHA.112.300818
    1. Sluijter JP, Verhage V, Deddens JC, van den AF, Doevendans PA. Microvesicles and exosomes for intracardiac communication. Cardiovasc Res. 2014;102: 302–311. 10.1093/cvr/cvu022
    1. Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension. 2004;43: 428–433.
    1. Viera AJ, Mooberry M, Key NS. Microparticles in cardiovascular disease pathophysiology and outcomes. J Am Soc Hypertens. 2012;6: 243–252. 10.1016/j.jash.2012.06.003
    1. Leroyer AS, Isobe H, Leseche G, Castier Y, Wassef M, Mallat Z, et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol. 2007;49: 772–777.
    1. Mallat Z, Hugel B, Ohan J, Leseche G, Freyssinet JM, Tedgui A. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation. 1999;99: 348–353.
    1. Morel O, Pereira B, Averous G, Faure A, Jesel L, Germain P, et al. Increased levels of procoagulant tissue factor-bearing microparticles within the occluded coronary artery of patients with ST-segment elevation myocardial infarction: role of endothelial damage and leukocyte activation. Atherosclerosis. 2009;204: 636–641. 10.1016/j.atherosclerosis.2008.10.039
    1. Min PK, Kim JY, Chung KH, Lee BK, Cho M, Lee DL, et al. Local increase in microparticles from the aspirate of culprit coronary arteries in patients with ST-segment elevation myocardial infarction. Atherosclerosis. 2013;227: 323–328. 10.1016/j.atherosclerosis.2013.01.032
    1. Empana JP, Boulanger CM, Tafflet M, Renard JM, Leroyer AS, Varenne O, et al. Microparticles and sudden cardiac death due to coronary occlusion. The TIDE (Thrombus and Inflammation in sudden DEath) study. Eur Heart J Acute Cardiovasc Care. 2014;2014[Epub ahead of print]
    1. Porto I, Biasucci LM, De Maria GL, Leone AM, Niccoli G, Burzotta F, et al. Intracoronary microparticles and microvascular obstruction in patients with ST elevation myocardial infarction undergoing primary percutaneous intervention. Eur Heart J. 2012;33: 2928–2938. 10.1093/eurheartj/ehs065
    1. Baars T, Konorza T, Kahlert P, Mohlenkamp S, Erbel R, Heusch G, et al. Coronary aspirate TNFalpha reflects saphenous vein bypass graft restenosis risk in diabetic patients. Cardiovasc Diabetol. 2013;12: 12 10.1186/1475-2840-12-12
    1. Kleinbongard P, Boese D, Konorza T, Steinhilber F, Moehlenkamp S, Eggebrecht H, et al. Acute vasomotor paralysis and potential downstream effects of paclitaxel from stents implanted for saphenous vein aorto-coronary bypass stenosis. Basic Res Cardiol. 2011;106: 681–689. 10.1007/s00395-011-0177-9
    1. Haude M, Caspari G, Baumgart D, Brennecke R, Meyer J, Erbel R. Comparison of myocardial perfusion reserve before and after coronary balloon predilation and after stent implantation in patients with postangioplasty restenosis. Circulation. 1996;94: 286–297.
    1. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group. N Engl J Med. 1985;312: 932–936.
    1. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37: 1478–1492.
    1. Boese D, von Birgelen C, Zhou XY, Schmermund A, Philipp S, Sack S, et al. Impact of atherosclerotic plaque composition on coronary microembolization during percutaneous coronary interventions. Basic Res Cardiol. 2008;103: 587–597. 10.1007/s00395-008-0745-9
    1. Leborgne L, Cheneau E, Pichard A, Ajani A, Pakala R, Yazdi H, et al. Effect of direct stenting on clinical outcome in patients treated with percutaneous coronary intervention on saphenous vein graft. Am Heart J. 2003;146: 501–506.
    1. Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37): 2541–2619. 10.1093/eurheartj/ehu278
    1. Horn P, Cortese-Krott MM, Amabile N, Hundsdorfer C, Kroncke KD, Kelm M, et al. Circulating microparticles carry a functional endothelial nitric oxide synthase that is decreased in patients with endothelial dysfunction. J Am Heart Assoc. 2013;2: e003764 10.1161/JAHA.112.003764
    1. Erdbrugger U, Rudy CK, Etter E, Dryden KA, Yeager M, Klibanov AL, et al. Imaging flow cytometry elucidates limitations of microparticle analysis by conventional flow cytometry. Cytometry A. 2014;85: 756–770. 10.1002/cyto.a.22494
    1. Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J. 2012;33(20): 2569–2619. 10.1093/eurheartj/ehs215
    1. Bernal-Mizrachi L, Jy W, Jimenez JJ, Pastor J, Mauro LM, Horstman LL, et al. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J. 2003;145: 962–970.
    1. Bonello L, Basire A, Sabatier F, Paganelli F, Dignat-George F. Endothelial injury induced by coronary angioplasty triggers mobilization of endothelial progenitor cells in patients with stable coronary artery disease. J Thromb Haemost. 2006;4: 979–981.
    1. Craft JA, Masci PP, Roberts MS, Brighton TA, Garrahy P, Cox S, et al. Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients. Blood Coagul Fibrinolysis. 2004;15: 475–482.
    1. George FD. Microparticles in vascular diseases. Thromb Res. 2008;122 Suppl 1: S55–S59. 10.1016/S0049-3848(08)70020-3
    1. Burnier L, Fontana P, Kwak BR, Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost. 2009;101: 439–451.
    1. Zhang Y, Liu X, Liu L, Zaske AM, Zhou Z, Fu Y, et al. Contact- and agonist-regulated microvesiculation of human platelets. Thromb Haemost. 2013;110: 331–339. 10.1160/TH12-11-0853
    1. Hamilos M, Muller O, Ntalianis A, Trana C, Bartunek J, Sarno G, et al. Relationship between peripheral arterial reactive hyperemia and residual platelet reactivity after 600 mg clopidogrel. J Thromb Thrombolysis. 2011;32: 64–71. 10.1007/s11239-011-0557-x
    1. Franca CN, Pinheiro LF, Izar MC, Brunialti MK, Salomao R, Bianco HT, et al. Endothelial progenitor cell mobilization and platelet microparticle release are influenced by clopidogrel plasma levels in stable coronary artery disease. Circ J. 2012;76: 729–736.
    1. Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS. Endothelium-derived microparticles impair endothelial funciton in vitro. Am J Physiol Heart Circ Physiol. 2004;286: H1910–H1915.
    1. Boulanger CM, Scoazec A, Ebrahimian T, Henry P, Mathiue E, Tedgui E, et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation. 2001;104: 2649–2652.
    1. Rautou PE, Leroyer AS, Ramkhelawon B, Devue C, Duflaut D, Vion AC, et al. Microparticles From Human Atherosclerotic Plaques Promote Endothelial ICAM-1-Dependent Monocyte Adhesion and Transendothelial Migration. Circ Res. 2011;108: 335–343. 10.1161/CIRCRESAHA.110.237420
    1. Zwicker JI, Trenor CC, III, Furie BC, Furie B. Tissue factor-bearing microparticles and thrombus formation. Arterioscler Thromb Vasc Biol. 2011;31: 728–733. 10.1161/ATVBAHA.109.200964
    1. Moons AH, Levi M, Peters RJ. Tissue factor and coronary artery disease. Cardiovasc Res. 2002;53: 313–325.
    1. Bonderman D, Teml A, Jakowitsch J, Adlbrecht C, Gyöngyösi M, Sperker W, et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood. 2002;99: 2794–2800.
    1. Mahemuti A, Meneveau N, Seronde MF, Schiele F, Descotes-Genon V, Ecarnot F, et al. Early changes in local hemostasis activation following percutaneous coronary intervention in stable angina patients: a comparison between drug-eluting and bare metal stents. J Thromb Thrombolysis. 2009;28: 333–341. 10.1007/s11239-008-0266-2
    1. Tutar E, Ozcan M, Kilickap M, Gulec S, Aras O, Pamir G, et al. Elevated whole-blood tissue factor procoagulant activity as a marker of restenosis after percutaneous transluminal coronary angioplasty and stent implantation. Circulation. 2003;108: 1581–1584.
    1. Mizuno O, Ikeda U, Hojo Y, Fujikawa H, Katsuki T, Shimada K. Tissue factor expression in coronary circulation as a prognostic factor for late restenosis after coronary angioplasty. Cardiology. 2001;95: 84–89.
    1. Jy W, Jimenez JJ, Mauro LM, Horstman LL, Cheng P, Ahn ER, et al. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost. 2005;3: 1301–1308.
    1. Jung F, Spitzer SG, Pindur G. Effect of an ionic compared to a non-ionic X-ray contrast agent on platelets and coagulation during diagnostic cardiac catheterisation. Pathophysiol Haemost Thromb. 2002;32: 121–126.

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