Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction.
BACKGROUND
Several reports showed an increase of CD34(+) stem/progenitor cell count early after an acute myocardial infarction (AMI), suggesting a contribution of bone marrow cells in myocardial regeneration after the acute event. Nevertheless, at present plasma mediators of CD34(+) cell mobilization from bone marrow to peripheral blood in patients with AMI are poorly understood. Aim of our study was to establish the impact of different well-known mobilizing cytokines on spontaneous stem cell mobilization in patients with different ischemic heart syndromes, such as the AMI and the chronic stable angina (CSA), compared to healthy controls.


METHODS
In 16 patients with AMI, 18 with CSA and 22 healthy blood donors the concentration of CD34(+) cells, and mobilizing cyokines (G-CSF, SCF, VEGF, SDF1-alpha) were assessed.


RESULTS
The peak number of circulating CD34(+) cells in AMI patients (8.58+/-2.08 cells/microl) was higher than that observed in patients with CSA (3.41+/-0.56 cells/microl, p=0.0061) or in healthy controls (2.18+/-0.35 cells/microl, p<0.001). However endogenous G-CSF was significantly higher in the serum of patients with AMI compared to CSA patients and to controls and in CSA patients compared to controls. Interestingly, as regards VEGF, while this cytokine was increased in AMI with respect to control and CSA group, the latter showed a significantly lower concentration with respect to controls. Finally SDF-1 alpha was higher in AMI patients with respect to controls. CD34(+) cells were significantly correlated to G-CSF (directly) and to SCF (inversely) in patients with AMI.


CONCLUSIONS
In the present study, we have demonstrated for the first time that the spontaneous mobilization of CD34(+) cells into the peripheral blood of patients with AMI is significantly correlated to endogenous G-CSF. Considering recent data suggesting a potential favourable effect of circulating CD34(+) cells on left ventricular function, the present evidence of a correlation between endogenous G-CSF and CD34(+) cell levels supports the pharmacological administration of G-CSF as a non-invasive option for regeneration of myocardial tissue after AMI.
Leone
Antonio Maria
AM
Institute of Cardiology, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy. antoniomarialeone@libero.it
Rutella
Sergio
S
Bonanno
Giuseppina
G
Contemi
Anna Maria
AM
de Ritis
Daniela G
DG
Giannico
Maria Benedetta
MB
Rebuzzi
Antonio G
AG
Leone
Giuseppe
G
Crea
Filippo
F
D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006321:Heart / Q000503:physiopathology; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D012016:Reference Values; D012038:Regeneration
D015703:Antigens, CD; D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor