title: CCL3 (MIP-1 alpha) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events.
abstract: As chemokines are considered instrumental in thrombotic plaque rupture and erosion as well as in ischemia-reperfusion injury processes, we aimed to identify previously unknown chemokines associated with acute coronary syndromes. Plasma of 44 patients with acute myocardial infarction (AMI) and 22 controls were profiled for a panel of chemokines by multiplex analysis. Levels of CCL3 were prospectively verified in 54 patients with unstable angina pectoris (UAP). An AMI mouse model was used to assess the relationship between differentially expressed chemokines and myocardial ischemia. CCL3 levels were significantly elevated in AMI vs. controls (P=0.02) albeit, that adjustment for confounding factors attenuated this association. In support of a direct association with cardiac ischemia CCL3 levels were also seen to be elevated in patients with UAP at baseline and significantly down-regulated after 180 days (P<0.001). Importantly, baseline upper quartile levels were strongly correlated with future acute coronary syndromes (Likelihood Ratio 11.5; P<0.01). Furthermore circulating levels of CCL3 were significantly enhanced after AMI in mice (P=0.02), while CCR5(+) T-cell numbers were increased as well, suggestive of CCL3 driven T-cell homing towards the ischemic area. CCL3 levels are elevated during ACS and released upon ischemia. Since CCL3 specifically predicts future cardiovascular events, it may serve as a predictive biomarker.
authors.affiliation: Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, PO Box 9502, 2300 RA Leiden, Leiden, The Netherlands. s.de.jager@lacdr.leidenuniv.nl
authors.forename: Saskia C A
authors.initials: SC
authors.lastname: de Jager
authors.forename: Adriaan O
authors.initials: AO
authors.lastname: Kraaijeveld
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grauss
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Su-San
authors.initials: SS
authors.lastname: Liem
authors.forename: Bas L
authors.initials: BL
authors.lastname: van der Hoeven
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D000789:Angina, Unstable / Q000097:blood; D000818:Animals; D054405:Chemokine CCL3 / Q000096:biosynthesis* / Q000097:blood; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D005544:Forecasting; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood / Q000175:diagnosis*; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3