on February 7, 2008
Published online before print February 7, 2008, doi: 10.1161/ATVBAHA.107.155333
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Submitted on September 3, 2007
Accepted on January 20, 2008
Prothrombotic Gene Expression Profile in Vascular Smooth Muscle Cells of Human Saphenous Vein, but not Internal Mammary Artery
S. K. Payeli ;
From Cardiovascular Research, Physiology Institute (S.K.P., R.L., C.G., T.F.L., F.C.T.), the Center for Integrative Human Physiology (S.K.P., R.L., C.G., T.F.L., F.C.T.), and the Functional Genomics Center Zurich (A.P., U.W.), University of Zurich, and Cardiology (C.G., T.F.L., F.C.T.), Cardiovascular Center, University Hospital Zurich, Switzerland.
* To whom correspondence should be addressed. E-mail: felix.tanner{at}access.uzh.ch.
Background—The resistance of internal mammary artery (IMA) toward thrombotic occlusion and accelerated atherosclerosis is not well understood. This study analyzed gene expression profiles of vascular smooth muscle cells (VSMCs) from IMA versus saphenous vein (SV).
Methods and Results—54'675 probe sets were examined by Affymetrix microarrays. Thirty-one genes belonged to the coagulation system; 2 were differentially expressed, namely tissue factor (TF) and tissue-type plasminogen activator (tPA). TF was 3.1-fold lower in IMA than SV (P=0.006), whereas tPA was 9.0-fold higher (P<0.001). TF mRNA expression was lower in IMA than SV (P<0.05); tPA was higher (P<0.001). TF protein expression was 4.2±0.5-fold lower in IMA than SV (P<0.001); tPA was 2.6±0.4-fold higher (P<0.01). In IMA VSMC supernatant, TF protein and activity was lower (P<0.05), TFPI and tPA protein higher (P<0.05 and P<0.005), and clotting time of human plasma prolonged (P<0.05) as compared to SV. Migration to TF/FVIIa (10-9 mol/L) was 3-fold lower in IMA than SV (P=0.01); PAR-2 protein expression was similar (P=NS), PAR-2 blockade without effect (P=NS).
Conclusions—Among the genes of the coagulation system, TF and tPA are differentially expressed in VSMCs from IMA versus SV. This is consistent with protection of IMA from thrombus formation and vascular remodeling.
Key words: bypass graft disease • tissue factor • tissue plasminogen activator • coagulation • migration