Filippo Crea Institute of Cardiology Catholic University of the Sacred Heart Rome, Italy Heartline...
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Transcript of Filippo Crea Institute of Cardiology Catholic University of the Sacred Heart Rome, Italy Heartline...
Filippo CreaInstitute of Cardiology
Catholic University of the Sacred HeartRome, Italy
HeartlineTrial sulla terapia cellulare:
end-point strumentali o clinici?
VEGF
G-CSF
C-KitMMP-9
CXCR4 CD
133CD
34
KDR C-Met
SD
F-1
HGFSCF
CXCR4
CD
34 KD
R
C-Met
C-K
it
C-K
it
CD 34+ cell mobilization in different coronary syndromes
AMI (n=54) CSA (n=26) Controls (n=43)0
10
20
30
40
p<0.001
p=0.036
p<0.001
CD
34+
cel
ls/m
l
(Leone et al, submitted to EHJ)
Effects of enalapril on long-term progression of left ventricular dysfunction in patients with heart
(SOLVD, Circulation 1992)
Room for improvement•Cell type •Cell preparation•Myocardial homing•Administration timing•Delivery method •Patient selection
Pharmacological BM-SC mobilizationDrugs Response
ACE-inhibitors ↑ EPC number
AT II antagonists ↑ EPC number
Statins ↑ EPC number
PPAR-gamma↑ EPC number↑ EPC functional activity
Insulin↑ EPC number↑ EPC clonogenic properties
Nitroglycerin Isosorbide-5-dinitrate
↑ EPC number↓ EPC migratory capacity
Pentaerythritol tetranitrate↑ EPC number↑ EPC migratory capacity
IGF-1
↑ EPC number↑ EPC differentiation↑ EPC migratory capacity↑ e-CFU
Growth Hormone↑ EPC number↑ EPC proliferation↑ EPC migration
Erythropoietin↑ EPC number↑ EPC proliferation↑ EPC adhesive properties
G-CSF ↑CD34+ cells↑ EPC number
Acute phase 5 days 4 months0
1
2
3
4
5
6
7
8Aggressive arm
Conservative arm
CD
34+
/KD
R+
EP
Cs
(n/m
l)
(Leone et al IJC 2008)
Targeted Migration of Mesenchymal Stem Cells Modified With CXCR4 Gene to Infarcted Myocardium Improves Cardiac Performance
(Cheng et al Mol Ther 2008)
Surrogate end-points: positive results• Flecainide in post-AMI
– Reduces ventricular ectopic beats– Increases mortality (CAST trial, NEJM 1991)
• Ibopamine in severe HF– Improves cardiac function– Increases mortality (PRIME II trial, Lancet 1997)
• Torcetrapib in dyslipedemia– Improves lipid profile– Increases mortality (ILLUMINATE, NEJM 2007)