Migratory activity of circulating progenitor cells and serum SDF-1α predict adverse events in patients with myocardial infarction

被引:43
作者
Fortunato, Orazio [1 ]
Spinetti, Gaia [1 ]
Specchia, Claudia [2 ]
Cangiano, Elisa [3 ]
Valgimigli, Marco [3 ]
Madeddu, Paolo [4 ]
机构
[1] IIRCCS MultiMed, Milan, Italy
[2] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy
[3] Univ Ferrara, I-44100 Ferrara, Italy
[4] Univ Bristol, Bristol Heart Inst, Sch Clin Sci, Bristol Royal Infirm, Bristol BS2 8HW, Avon, England
基金
英国医学研究理事会;
关键词
Acute myocardial infarction; Migration; Circulating progenitor cells; SDF-1; alpha; C-MET(+) STEM-CELLS; BONE-MARROW; PERIPHERAL-BLOOD; MOBILIZATION; NEOVASCULARIZATION; FACTOR-1-ALPHA; MUSCLE; RISK; TRAFFICKING; CONTRIBUTES;
D O I
10.1093/cvr/cvt153
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Following acute myocardial infarction (AMI), pro-angiogenic progenitor cells (PCs) are released from the bone marrow into the circulation and home to the ischaemic site attracted by a chemokine gradient. It is unknown if components of this early homeostatic response might help forecast the long-term clinical outcome. This study investigates if the number and migratory activity of circulating PCs predict adverse events in patients with AMI (clinical trial: NCT01271309). Basal counts and in vitro migratory activity of CD34/CD45/CD133/CXCR4 PCs and serum cytokine levels were assessed during the first 5 days after AMI in a consecutive series of 172 patients. Clinical outcomes of the study were death, repeat AMI, and new-onset heart failure at a 1-year follow-up. The association between PC counts and cytokine levels with the incidence of clinical outcomes was assessed by multivariable regression models. AMI patients who underwent an event showed higher serum stromal cell-derived factor 1 (SDF-1) levels and reduced spontaneous motility of PCs in an in vitro migration assay when compared with event-free subjects. After adjustment for age, gender, the presence or absence of ST elevation, or diabetes, the percentage of PCs non-migrated towards vehicle or SDF-1 were both independent predictors of death or repeat AMI and new-onset heart failure (odds ratio [OR] 2, P 0.015 and OR 1.90, P 0.018, respectively). Moreover, serum SDF-1 levels predict adverse events (OR 3.8, P 0.007). Biomarkers reflecting the migratory activity of circulating PCs may aid the assessment of secondary risk in AMI patients.
引用
收藏
页码:192 / 200
页数:9
相关论文
共 44 条
[1]
The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques [J].
Abi-Younes, S ;
Sauty, A ;
Mach, F ;
Sukhova, GK ;
Libby, P ;
Luster, AD .
CIRCULATION RESEARCH, 2000, 86 (02) :131-138
[2]
Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes [J].
Antman, EM ;
Tanasijevic, MJ ;
Thompson, B ;
Schactman, M ;
McCabe, CH ;
Cannon, CP ;
Fischer, GA ;
Fung, AY ;
Thompson, C ;
Wybenga, D ;
Braunwald, E .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (18) :1342-1349
[3]
VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells [J].
Asahara, T ;
Takahashi, T ;
Masuda, H ;
Kalka, C ;
Chen, DH ;
Iwaguro, H ;
Inai, Y ;
Silver, M ;
Isner, JM .
EMBO JOURNAL, 1999, 18 (14) :3964-3972
[4]
Human CD133+ Progenitor Cells Promote the Healing of Diabetic Ischemic Ulcers by Paracrine Stimulation of Angiogenesis and Activation of Wnt Signaling [J].
Barcelos, Luciola S. ;
Duplaa, Cecile ;
Kraenkel, Nicolle ;
Graiani, Gallia ;
Invernici, Gloria ;
Katare, Rajesh ;
Siragusa, Mauro ;
Meloni, Marco ;
Campesi, Ilaria ;
Monica, Manuela ;
Simm, Andreas ;
Campagnolo, Paola ;
Mangialardi, Giuseppe ;
Stevanato, Lara ;
Alessandri, Giulio ;
Emanueli, Costanza ;
Madeddu, Paolo .
CIRCULATION RESEARCH, 2009, 104 (09) :1095-U199
[5]
Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction - Feasibility and safety [J].
Bartunek, J ;
Vanderheyden, M ;
Vandekerckhove, B ;
Mansour, S ;
De Bruyne, B ;
De Bondt, P ;
Van Haute, I ;
Lootens, N ;
Heyndrickx, G ;
Wijns, W .
CIRCULATION, 2005, 112 (09) :I178-I183
[6]
Cells as biologics for cardiac repair in ischaemic heart failure [J].
Bartunek, Jozef ;
Vanderheyden, Marc ;
Hill, Jonathan ;
Terzic, Andre .
HEART, 2010, 96 (10) :792-800
[7]
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1 [J].
Ceradini, DJ ;
Kulkarni, AR ;
Callaghan, MJ ;
Tepper, OM ;
Bastidas, N ;
Kleinman, ME ;
Capla, JM ;
Galiano, RD ;
Levine, JP ;
Gurtner, GC .
NATURE MEDICINE, 2004, 10 (08) :858-864
[8]
Role of Stromal Cell-Derived Factor-1α, Level and Value of Circulating Interleukin-10 and Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Angioplasty [J].
Chang, Li-Teh ;
Yuen, Chun-Man ;
Sun, Cheuk-Kwan ;
Wu, Chiung-Jen ;
Sheu, Jiunn-Jye ;
Chua, Sarah ;
Yeh, Kuo-Ho ;
Yang, Cheng-Hsu ;
Youssef, Ali A. ;
Yip, Hon-Kan .
CIRCULATION JOURNAL, 2009, 73 (06) :1097-1104
[9]
Effects of CXCR4 Gene Transfer on Cardiac Function After Ischemia-Reperfusion Injury [J].
Chen, Jiqiu ;
Chemaly, Elie ;
Liang, Lifan ;
Kho, Changwon ;
Lee, Ahyoung ;
Park, Jaeho ;
Altman, Perry ;
Schecter, Alison D. ;
Hajjar, Roger J. ;
Tarzami, Sima T. .
AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (04) :1705-1715
[10]
Stromal cell-derived factor-1α in unstable angina -: Potential antiinflammatory and matrix-stabilizing effects [J].
Damås, JK ;
Wæhre, T ;
Yndestad, A ;
Ueland, T ;
Müller, F ;
Eiken, HG ;
Holm, AM ;
Halvorsen, B ;
Froland, SS ;
Gullestad, L ;
Aukrust, P .
CIRCULATION, 2002, 106 (01) :36-42