title: Circulating cells as predictors of secondary manifestations of cardiovascular disease: design of the CIRCULATING CELLS study.
abstract: Biomarkers for primary or secondary risk prediction of cardiovascular disease (CVD) are urgently needed to improve individual treatment and clinical trial design. The vast majority of biomarker discovery studies has concentrated on plasma/serum as an easily accessible source. Although numerous markers have been identified, their added predictive value on top of traditional risk factors has been limited, as the biological specimen does not specifically reflect expression profiles related with CVD progression and because the signal is often diluted by marker release from other organs. In contrast to serum markers, circulating cells serve as indicators of the actual disease state due to their active role in the pathogenesis of CVD and are responsible for the majority of secreted biomarkers. Therefore, the CIRCULATING CELLS study was initiated, focusing on the cellular effectors of atherosclerosis in the circulation. In total, 714 patients with coronary artery disease (CAD) symptoms were included. Blood cell fractions (monocytes, T-lymphocytes, platelets, granulocytes, PBMC) of all individual patients were isolated and stored for analysis. Concomitantly, extensive flow cytometric characterization of these populations was performed. From each patient, a detailed clinical profile together with extensive questionnaires about medical history and life style was obtained. Various high-throughput -omics approaches (protein, mRNA, miRNA) are currently being undertaken. Data will be integrated with advanced bioinformatics for discovery and validation of secondary risk markers for adverse events. Overall, the CIRCULATING CELLS study grants the interesting possibility that it will both identify novel biomarkers and provide useful insights into the pathophysiology of CAD in patients.
authors: Laboratory of Experimental Cardiology, UMC Utrecht, Room G02.523, Heidelberglaan 100, 3584, Utrecht, CX, The Netherlands, i.hoefer@umcutrecht.nl.
authors: Imo E
authors: IE
authors: Hoefer
authors: Jan-Willem
authors: JW
authors: Sels
authors: J Wouter
authors: JW
authors: Jukema
authors: Sandrin
authors: S
authors: Bergheanu
authors: Erik
authors: E
authors: Biessen
authors: Elizabeth
authors: E
authors: McClellan
authors: Mat
authors: M
authors: Daemen
authors: Pieter
authors: P
authors: Doevendans
authors: Philip
authors: P
authors: de Groot
authors: Marieke
authors: M
authors: Hillaert
authors: Sebastiaan
authors: S
authors: Horsman
authors: Mustafa
authors: M
authors: Ilhan
authors: Johan
authors: J
authors: Kuiper
authors: Nico
authors: N
authors: Pijls
authors: Ken
authors: K
authors: Redekop
authors: Peter
authors: P
authors: van der Spek
authors: Andrew
authors: A
authors: Stubbs
authors: Eric
authors: E
authors: van de Veer
authors: Johannes
authors: J
authors: Waltenberger
authors: Anton-Jan
authors: AJ
authors: van Zonneveld
authors: Gerard
authors: G
authors: Pasterkamp
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers
references: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1433-8
references: 19229072
references: Circulation. 2003 Oct 14;108(15):1772-8
references: 14557340
references: Expert Rev Cardiovasc Ther. 2004 Jul;2(4):535-45
references: 15225113
references: Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3423-8
references: 15728378
references: N Engl J Med. 2005 Sep 8;353(10):999-1007
references: 16148285
references: Clin Res Cardiol. 2013 Jul;102(7):495-503
references: 23519584
references: J Clin Invest. 2005 Dec;115(12):3378-84
references: 16322783
references: Eur Heart J. 2002 Aug;23(15):1177-89
references: 12127920
references: Clin Chem Lab Med. 2004 Mar;42(3):273-8
references: 15080559
references: EuroIntervention. 2005 Aug;1(2):219-27
references: 19758907
references: Eur Heart J. 2012 Dec;33(23):2970-9
references: 22942337
references: Circulation. 2005 May 24;111(20):2654-61
references: 15883205
references: Clin Res Cardiol. 2012 Apr;101(4):247-53
references: 22116101
references: Cardiovasc Res. 2009 Jan 1;81(1):11-9
references: 18818214
references: Circ Res. 2008 Feb 1;102(2):209-17
references: 17991882
references: Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1506-16
references: 21677293
references: Circulation. 2003 Oct 7;108(14):1664-72
references: 14530185
references: JAMA. 2001 Nov 7;286(17):2107-13
references: 11694151
references: Nat Rev Immunol. 2006 Jul;6(7):508-19
references: 16778830
references: Circulation. 2005 Jan 18;111(2):212-21
references: 15630028
references: Eur Heart J. 2008 Aug;29(16):1966-74
references: 18621771
references: Nephrol Dial Transplant. 2010 Jul;25(7):2265-72
references: 20150168
references: Transl Res. 2012 Apr;159(4):265-76
references: 22424430
references: Clin Chem Lab Med. 2007;45(9):1109-20
references: 17635069
references: Circulation. 2004 Dec 21;110(25):3815-21
references: 15583081
references: Circulation. 2005 Jun 7;111(22):2981-7
references: 15927972
references: J Proteome Res. 2012 Nov 2;11(11):5235-44
references: 23020738
references: J Am Coll Cardiol. 2009 Dec 1;54(23):2129-38
references: 19942084
references: Coron Artery Dis. 2003 Sep;14(6):431-8
references: 12966263
references: J Card Fail. 2009 Nov;15(9):747-55
references: 19879460
references: JAMA. 2008 Feb 6;299(5):547-54
references: 18252885
references: Thromb Haemost. 2004 Aug;92(2):419-24
references: 15269840
references: Circulation. 2002 May 7;105(18):2166-71
references: 11994250
references: J Mol Cell Cardiol. 2009 Feb;46(2):177-85
references: 19059264
references: Clin Res Cardiol. 2013 Apr;102(4):249-57
references: 23117697
references: N Engl J Med. 2009 Jan 15;360(3):213-24
references: 19144937
references: J Thromb Haemost. 2010 May;8(5):906-13
references: 20128867
references: Circ Res. 2007 Jan 5;100(1):27-40
references: 17204662
references: Ann Med. 2012 Aug;44(5):433-47
references: 21623699
references: N Engl J Med. 2007 Apr 12;356(15):1503-16
references: 17387127
references: Eur J Epidemiol. 2004;19(12):1127-33
references: 15678794
references: Arterioscler Thromb Vasc Biol. 2008 May;28(5):947-53
references: 18292391
references: J Mol Cell Cardiol. 2003 Aug;35(8):993-8
references: 12878486
references: N Engl J Med. 2009 Mar 5;360(10):961-72
references: 19228612
references: Trends Cardiovasc Med. 2006 Jul;16(5):163-8
references: 16781950
references: Kidney Int. 2008 Mar;73(5):622-9
references: 18160960
references: Int J Biochem Cell Biol. 2010 Nov;42(11):1762-6
references: 20673808
references: Clin Res Cardiol. 2013 Feb;102(2):103-10
references: 22886030
references: Eur Heart J. 2008 Nov;29(22):2713-22
references: 18765457
references: N Engl J Med. 2012 Oct 4;367(14):1310-20
references: 23034020
references: Atherosclerosis. 2010 Oct;212(2):628-35
references: 20615506
references: Eur Heart J. 2002 Aug;23(15):1190-201
references: 12127921
references: Circulation. 1996 Sep 1;94(5):874-7
references: 8790019
references: Eur Heart J. 2011 May;32(10):1214-26
references: 21217142
references: N Engl J Med. 2006 Dec 21;355(25):2631-9
references: 17182988
references: Int J Cardiol. 2009 Jun 12;135(1):27-35
references: 18590932