Isoforms of apolipoprotein E can modulate tPA-induced clot lysis in vitro.
Apo E, and its respective isoforms, have been linked to outcome and survival in cerebral vascular and cardiovascular diseases. The effectiveness of intravenous tPA in patients with acute ischemic stroke appears to be enhanced in patients who have an Apo E2 phenotype. The ability of Apo E isoproteins (endogenous Apo E isoproteins or exogenous Apo E isoproteins) to modulate tPA-induced clot lysis in vitro was assessed using an in vitro clot assay system. Blood samples were obtained from 18-volunteers with three Apo E genotypes: E2, E3 and E4. tPA-induced clot lysis (0-4 microgram/ml tPA), was assessed in the presence or absence of supplemental Apo E2, E3 or E4 (9.8 microgram/ml). tPA-induced clot lysis was significantly (P equal or less than 0.0001) enhanced by supplementation with Apo E2 (EC50 0.20 0.06 microgram/ml) as compared to tPA alone (0.72 0.19). Apo E4 supplementation caused a significant (P < or = 0.05) inhibition of clot lysis (0.98 0.23), but there was no significant change caused by Apo E3. The genotype of the volunteer did not significantly affect the ability of the supplemental Apo E from modulating tPA-induced clot lysis. We conclude that the administration of Apo E isoproteins can modulate clot lysis in vitro. Our results suggest that the Apo E isoprotein may have an impact on clot dissolution and the effectiveness of thrombolytic therapy.
The Neuroscience Institute, Department of Neurology, University of Cincinnati College of Medicine, The Vontz Center for molecular Studies, Cincinnati, Ohio 45267-0536, USA. joseph.clark@uc.edu
Joseph F
JF
Clark
Daniel A
DA
Huri
Janice
J
Carrozzella
Edward C
EC
Jauch
Pritesh
P
Mehta
Daniel
D
Heaton
Susan J
SJ
Biehle
Joseph P
JP
Broderick
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002855:Chromatography, Thin Layer / Q000379:methods; D005342:Fibrinolysis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D006801:Humans; D009061:Mouth Mucosa / Q000737:chemistry; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020033:Protein Isoforms; D010959:Tissue Plasminogen Activator