ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Claus Bartels
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Christiansen, J. F.
Right arrow Articles by Bartels, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Christiansen, J. F.
Right arrow Articles by Bartels, C.
Related Collections
Right arrow Coronary disease

Ann Thorac Surg 2004;77:1575-1579
© 2004 The Society of Thoracic Surgeons

Original article: cardiovascular

Diseased vein grafts express elevated inflammatory cytokine levels compared with atherosclerotic coronary arteries

Jan Felix Christiansen, MDa*, Dirk Hartwig, MDb, J.F. Matthias Bechtel, MDa, Harald Klüter, MDc, Hans- H. Sievers, MDa, Uwe Schönbeck, PhDd, Claus Bartels, MDa

a Department of Cardiac Surgery, Lübeck, Germany
b Institute for Immunology and Transfusion Medicine, University Hospital, Lübeck, Germany
c Institute of Transfusion Medicine and Clinical Immunology Mannheim, Red Cross Blood Service of Baden-Württemberg, Mannheim, Germany
d Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

Accepted for publication October 16, 2003.

* Address reprint requests to Dr Christiansen, Klinik für Herzchirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
e-mail: janfelixchristiansen{at}gmx.de


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 References
 
BACKGROUND: The pathologic modifications characterizing vein graft disease resemble those observed in native arteriosclerosis, but in accelerated form. Although both disorders are considered to be inflammatory diseases, it remains to be determined whether diseased vein grafts and atherosclerotic coronary arteries differentially express inflammatory mediators. Therefore, we examined whether differences in the expression of proinflammatory cytokines by these two distinct vascular pathologies favor the accelerated inflammation within diseased vein grafts.

METHODS: The messengerRNA expression of various cytokines (interleukin-1ß [IL-1ß], IL-6, IL-8, tumor necrosis factor-{alpha} [TNF-{alpha}], interferon-{gamma} [IFN-{gamma}]) was quantified using real-time reverse transcriptase–polymerase chain reaction (RT-PCR) in tissue samples of native saphenous veins (NSV, n = 5), diseased coronary arteries (CAD, n = 25), and diseased vein grafts (VG, n = 13).

RESULTS: Native saphenous veins did not contain any detectable transcripts except for IFN-{gamma}. As expected, CAD was characterized by the expression of IL-1ß, IL-6, IL-8, IFN-{gamma}, and TNF-{alpha} mRNA. Interestingly VG also expressed these mediators, but at markedly higher levels. Quantification by RT-PCR revealed that, compared with specimens from the CAD group, VG specimens contained 5.8 ± 1.2 times, 286 ± 22 times, and 29 ± 7.3 times as many transcripts for the cytokines IL-1ß, IL-6 and TNF-{alpha}, respectively, as well as 25 ± 8.3 times more transcripts for the chemokine IL-8. In contrast, the expression of IFN-{gamma} transcripts did not differ among the groups.

CONCLUSIONS: The elevated expression of proinflammatory cytokine transcripts supports the hypothesis that diseased vein grafts, compared with atherosclerotic coronary arteries, are characterized by enhanced inflammatory activity that might accelerate atherosclerotic modifications. This may implicate new therapeutic strategies for the prevention of vein graft disease.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 References
 
Coronary artery bypass grafting has been used to treat myocardial ischemic disease for more than three decades. Failure of coronary artery venous grafts occurs at a substantial rate and has a major impact on survival. Indeed, as many as 50% of coronary artery grafts fail within 10 years after coronary artery bypass grafting (CABG), some as early as several months after surgery. Histologically, diseased vein grafts are characterized by atherosclerotic modifications. Although they share several characteristics of chronic inflammatory sites, diseased vein grafts are morphologically distinct from native atherosclerotic plaques, displaying higher infiltration by immunocompetent cells, such as macrophages, granulocytes and lymphocytes, as well as a poorly developed or absent fibrous cap [1].

Much of the understanding of the pathogenesis of vein graft disease is extrapolated from studies on atherogenesis in coronary arteries. Native arteriosclerosis is considered a chronic inflammatory disease in which the cytokine network plays a central role [2, 3]. Whether a cytokine-mediated chronic inflammatory process also plays a pathogenetic role in vein graft disease is not known. The cytokines interleukin-1 (IL-1), IL-6, tumor necrosis factor-(TNF-{alpha}), interferon-{gamma} (IFN-{gamma}), and the chemokine IL-8 are associated with several pathogenic processes underlying arteriosclerosis. These processes are also observed in diseased vein grafts, although in accelerated form. Among other processes, these cytokines modulate smooth muscle cell proliferation/apoptosis and inhibit smooth muscle cell production of fibrilar collagen and other extracellular matrix components crucial for the integrity of atherosclerotic lesions. Moreover, in numerous atheroma-associated cell types they stimulate the production of matrix-degrading proteinases that assist in the breakdown of collagen and elastin, thus further promoting the vulnerability of plaque to rupture [3].

To test this hypothesis, we used real-time reverse transcriptase–polymerase chain reaction (RT-PCR) to quantify the expression of transcripts for the cytokines of IL-1ß, IL-6, TNF-{alpha}, IFN-{gamma}, and the chemokine IL-8 in RNA preparations obtained from atherosclerotic coronary arteries, diseased vein grafts (VG), and native saphenous veins (NSV). Detection of transcript expression was chosen to illuminate actively pursued inflammatory/immune responses in the vessel wall rather than reflecting simple accumulation of deposited proteins.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 References
 
Specimens of atherosclerotic coronary arteries (CAD group, n = 25), diseased vein grafts (VG group, n = 13) and native, nondiseased human saphenous veins (NSV group, n = 5) were obtained from donors matched for gender, age, body mass index, smoking history, diabetes, hypertension, and hyperlipidemia (Table 1). All donors have given informed consent and the study was approved by the local ethics committee. Parts from NSVs and diseased coronary arteries were obtained from 25 patients during primary coronary artery bypass procedures at the clinic for cardiac surgery, University Hospital Lübeck. The indication for the removal of diseased coronary arteries was the intraoperative finding that a segment of the coronary artery selected for bypass grafting exhibited a pronounced vessel wall calcification or a subtotal vessel occlusion not allowing standard end-to-side anastomosis to the native saphenous vein. In this case the calcified coronary vessel wall was dissected from the smooth adventitial layer in accordance with our routine procedure to allow the establishment of the anastomosis (technique comparable to carotid endarterectomy).


View this table:
[in this window]
[in a new window]
  		Table 1. Patient Characteristics

 
Diseased vein grafts were obtained from 13 patients with relapsed symptomatic CAD undergoing repeat coronary bypass surgery at the clinic for cardiac surgery, University Hospital Lübeck. The indication for removal of diseased vein grafts, which is not part of the redo coronary bypass surgery routine, was the risk of subsequent embolization of atherosclerotic material from the vein grafts into the coronary circulation. In all patients new venous bypass grafts were anastomized to the target coronary artery. The segment of the old vein graft that was removed and taken for analysis was the worst, most severely stenosed part. Before obtaining the specimen first cardioplegia was given.

Preliminary studies indicated that freezing of tissue samples following an interval more than 3 minutes after surgical removal did not allow for the successful isolation of cytokine mRNA due to rapid degradation. The procedure was then modified by making liquid nitrogen available in the operating theater to allow snap freezing of all atherosclerotic arteries, diseased vein grafts, and human saphenous veins in liquid nitrogen less than 5 seconds after removal. The specimens were subsequently stored at –70°C until RNA isolation.

Additionally, in each specimen group semiquantitative morphologic cytology (HE stain) was examined for polymorph granulocytes and for lymphocytes.

Quantification of mRNA
Fifty milligrams to 100 mg of the respective tissue specimen were minced and total RNA was isolated using the Purescript RNA Isolation Kit (Gentra Systems, Minneapolis, MN), according to the manufacturer's protocol. Cytokine mRNA/transcripts were quantified by RT-PCR (ABI Prism 7700 Sequence Detection System; Applied Biosystems, Foster City, CA) according to the protocol recently reported by Hartwig and colleagues [4], and using the exon/intron spanning primers (TIB Molbiol, Berlin, Germany) outlined in Table 2. Briefly, 20 U RNAse-Inhibitor (Pharmacia, Piscataway, NJ) and 25 U murine leukemia virus (MuLV) reverse transcriptase (Perkin-Elmer Cetus, Wellesley, MA) were added to the PCR reaction mixture containing 5 µL 10x Taq human A-Buffer (Perkin-Elmer Cetus), 2.5 mmol/L MgCl2, 300 µmol/L dATP, dCTP, dGTP, 600 µmol/L dUTP, 100 nmol/L of forward and reverse primer, 100 nmol/L fluorogenic probe, 1.25 U Ampli-Taq Gold-DNA-Polymerase (Perkin-Elmer Cetus), and RNA sample in a volume of 50 µL. The reverse-transcriptase-PCR conditions were 30 min at 48°C for reverse transcription, 10 minutes at 95°C, and followed by 40 cycles of 15 seconds at 95°C and 90 seconds at 60°C. Controls included mock PCR reactions performed in the absence of the reverse transcriptase or using water as template.


View this table:
[in this window]
[in a new window]
  		Table 2. Primer and Probe Sequences

 
Serial logarithmic dilutions of ß–actin or cytokine standard RNA [4, 5] with known amounts of molecules were prepared in triplicate to generate standard curves. The copy numbers of cytokine and ß-actin mRNA were derived by interpolation from the standard curves. The ratio between cytokine and ß-actin mRNA provides the normalized cytokine mRNA expression.

Statistical analysis
Patient characteristics of the groups were compared using ANOVA (age and body mass index) and X2 tests (dichotomous variables). Cytokine levels were found to be nonnormal and, thus, were compared using the nonparametric Mann-Whitney test. Because the cytokine data were highly skewed, they were summarized using medians and ranges and the transformation log (1 + cytokine level) was used when displaying the data graphically. A p value of less than 0.05 was considered significant. The Minitab software package (Minitab Inc, State College, PA) was used for statistical analyses.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 References
 
Specimens in the NSV group did not express detectable mRNA for the proinflammatory cytokines IL-1ß, IL-6, and TNF-{alpha} or the chemokine IL-8 (Table 3). As expected, transcripts for these mediators were detected in tissue of human atherosclerotic coronary arteries (Table 3). Interestingly, mRNA for IL-1ß, IL-6, IL-8, and TNF-{alpha} was also detected at markedly elevated levels in specimens from the VG group (Table 3). Although the median levels of IL-6 and TNF-{alpha} in the CAD group were both zero due to the statistical calculation (Table 3), cytokine mRNA was detected as revealed by the mean ± standard deviation data. Quantification by real-time RT-PCR indicated that, compared with specimens from CAD group, VG specimen contained 5.8 ± 1.2 (p = 0.012), 286 ± 22.3 times (p = 0.0004), and 29 ± 7.3 times (p = 0.023) more transcripts for the cytokines IL-1ß, IL-6, and TNF-{alpha}, respectively, as well as 25 ± 8.3 times (p = 0.001) more transcripts for the chemokine IL-8 (Fig 1). Interestingly, the signals obtained for IFN-{gamma} transcripts did not differ between the groups (Table 3 and Fig 1). Control experiments using nonreverse transcribed RNA preparations detected no signals for any of the cytokines analyzed (data not shown).


View this table:
[in this window]
[in a new window]
  		Table 3. Medians and Ranges of mRNA Cytokine Expression for Each Cytokine

 


View larger version (31K):
[in this window]
[in a new window]
  		Fig 1. Content of mRNA copies of each cytokine. Values are given in ln (1x106 copies of mRNA expression of each cytokine). Dark shaded bars = nondiseased, native saphenous vein group; medium-shaded bars = atherosclerotic coronary artery disease group; light shaded bars = diseased vein graft group. (IL-1 = interleukin-1; IL-6 = interleukin-6; IL-8 = interleukin-8; INF-{gamma} = interferon-gamma; TNF-{alpha} = tumor necrosis factor-alpha.)

 
Like the proinflammatory cytokines, T lymphocytes, thought to be major players in atherogenesis, were found to be increased in VG versus CAD specimens, the diseased VG specimens exhibiting 2.8 ± 0.9 times greater levels (Table 4). As expected, NSV specimens contained no detectable T lymphocytes. Notably, macrophage counts did not differ between the two diseased groups.


View this table:
[in this window]
[in a new window]
  		Table 4. Accumulation of T Lymphocytes and Macrophages

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
References
 
The present study demonstrates enhanced mRNA expression of the proinflammatory cytokines IL-1ß, IL-6, and TNF-{alpha}, as well as of the chemokine IL-8 in human diseased vein grafts compared with diseased coronary arteries. This phenomenon may indicate greater inflammatory activity in vein graft disease, potentially contributing to the accelerated form of arteriosclerosis observed in this clinical complication.

The elevated expression of cytokine transcripts we found in atherosclerotic coronary arteries is in accord with the findings in previous studies.

During atherogenesis these mediators promote numerous pathogenic processes that are also implicated in diseased vein grafts [2, 6–10]. Like native arteriosclerosis in coronary arteries, vein grafts respond to endothelial injury with intimal hyperplasia, which is mediated by the migration and proliferation of smooth muscle cells and eventually produces a neointima. Neointima formation is considered one of the potential pathogenic mechanisms underlying vein graft disease. This process involves the proliferation and migration of vascular smooth muscle cells, macrophages, lymphocytes, and endothelial cells [11]. Two of the cytokines we analyzed, IL-1ß and TNF-{alpha}, are established mitogens for this cell type and have also been implicated in the migration of neointimal smooth muscle cells [8] and the formation of intimal hyperplasia [3, 12]. These cytokines as well are identified as stimulators of the production of endothelin-1, a marker for many pathologic and inflammatory conditions in the vessel wall [13]. Enhanced inflammation induced no changes in levels of IFN-{gamma}, an established inhibitor of smooth muscle cell proliferation, which further supports the hypothesis that increased expression of this set of proinflammatory cytokines promotes accelerated arteriosclerosis. The accumulation of an inflammatory infiltrate composed predominantly of T lymphocytes and monocytes is another characteristic of atherosclerotic lesions [2]. Several of the cytokines that are elevated in diseased vein grafts also participate in these processes, either indirectly by inducing the expression of adhesion molecules [12, 14–16], as is the case with IL-1ß and TNF-{alpha}, or directly by acting as a chemoattractant for T cells and macrophages, as is the case with IL-8 [17]. The expression of CD40 molecule on dendritic cells in the vessel wall which regulate T-cell response [18] might be affected as well by these cytokines.

Since during thrombendarteriectomy of the coronary artery only parts from the intima and media were taken for our analysis one could assume that some of the cytokine mRNA is left in the adventitia of the artery. However inflammation during arteriosclerosis mainly takes part in the intima and media. More recently coworkers from our group [19] have performed immunostaining for C-reactive protein in diseased coronary arteries. An example is given in Figure 2. It shows that cytoplasmic C-reactive protein immunoreactivity is limited to the neointima and the media, which also demonstrate massive proliferation of foam cells and spindlelike smooth muscle cells. Adventitia only revealed little staining for C-reactive protein. Therefore, we think that eventually remaining inflammatory cytokine mRNA in the adventitial part of the coronary artery can be disregarded for our analysis.



View larger version (167K):
[in this window]
[in a new window]
  		Fig 2. Immunostaining for C-reactive protein in a diseased coronary artery (100-fold magnified). Neointima formation reveals massive proliferation of foam cells and spindlelike smooth muscle cells. Cytoplasmic C-reactive protein immunoreactivity is limited to smooth muscle cells of the neo-intima and the media. Adventitial tissue reveals only little staining.

 
In the present study, the amount of IFN-{gamma} transcripts did not differ between the NSV group and the CAD and VG group. Among the possible explanations for this finding is the preexisting phlebosclerosis in the native saphenous veins, which possibly leads to increased expression of IFN-{gamma} mRNA. In this context it seems noteworthy that most saphenous veins used for grafts are not obtained from healthy individuals, but are taken from a diseased portion of the venous vascular tree obtained from atherosclerotic patients. Intimal thickening due to preexisting phlebosclerosis affects up to 95% of saphenous veins in the sixth and seventh decades of life [20].

In summary, the present study demonstrates that the expression of transcripts for the proinflammatory cytokines IL-1ß, IL-6, and TNF-{alpha}, and for the chemokine IL-8 is greater in diseased vein grafts than in atherosclerotic coronary arteries. It remains for future studies to determine whether this phenomenon indeed is a fundamental pathophysiologic condition for the accelerated arteriosclerosis in diseased vein grafts.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Neitzel G.F., Barboriak J.J., Pintar K., Qureshi I. Atherosclerosis in aortocoronary bypass grafts. Morphologic study and risk factor analysis 6 to 12 years after surgery. Arteriosclerosis 1986;6:594-600.[Abstract]
  2. Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med 1999;340:115-126.[Free Full Text]
  3. Libby P., Warner S.J., Friedman G.B. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest 1988;81:487-498.
  4. Hartwig D., Härtel C., Hennig H., Müller-Steinhardt M., Schlenke P., Klüter H. Evidence for de-novo synthesis of cytokines and chemokines in platelet concentrates. Vox Sanguinis 2002;82:182-190.[Medline]
  5. Hartel C., Bein G., Kirchner H., Kluter H. A human whole-blood assay for analysis of T-cell function by quantification of cytokine mRNA. Scand J Immunol 1999;49:649-654.[Medline]
  6. Crook M.F., Newby A.C., Southgate K.M. Expression of intercellular adhesion molecules in human saphenous veins: effects of inflammatory cytokines and neointima formation in culture. Atherosclerosis 2000;150:33-41.[Medline]
  7. Frostegard J., Ulfgren A.K., Nyberg P., Hedin U., Swedenborg J., Andersson U., Hansson G.K. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 1999;145:33-43.[Medline]
  8. Barillari G., Albonici L., Incerpi S., et al. Inflammatory cytokines stimulate vascular smooth muscle cells locomotion and growth by enhancing alpha5beta1 integrin expression and function. Atherosclerosis 2001;154:377-385.[Medline]
  9. Clinton S.K., Libby P. Cytokines and growth factors in atherogenesis. Arch Pathol Lab Med 1992;116:1292-1300.[Medline]
  10. Motwani J.G., Topol E.J. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998;97:916-931.[Abstract/Free Full Text]
  11. Hilker M., Tellmann G., Buerke M., et al. Proliferative activity in stenotic human aortocoronary bypass grafts. Cardiovasc Pathol 2002;11:284-290.[Medline]
  12. Rectenwald J.E., Moldawer L.L., Huber T.S., Seeger J.M., Ozaki C.K., Malcom R. Direct evidence for cytokine involvement in neointimal hyperplasia. Circulation 2000;102:1697-1702.[Abstract/Free Full Text]
  13. Woods M., Bishop-Bailey D., Pepper J.R., Evans T.W., Mitchell J.A., Warner T.D. Cytokine and lipopolysaccharide stimulation of endothelin-1 release from human internal mammary artery and saphenous vein smooth-muscle cells. J Cardiovasc Pharmacol 1998;31(Suppl 1):348-350.
  14. Couffinhal T., Duplaa C., Moreau C., Lamaziere J.M., Bonnet J. Regulation of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular smooth muscle cells. Circ Res 1994;74:225-234.[Abstract/Free Full Text]
  15. Wyble C.W., Hynes K.L., Kuchibhotla J., Marcus B.C., Hallahan D., Gewertz B.L. TNF-alpha and IL-1 upregulate membrane-bound and soluble E-selectin through a common pathway. J Surg Res 1997;73:107-112.[Medline]
  16. Libby P., Tanaka H. The molecular bases of restenosis. Prog Cardiovasc Dis 1997;40:97-106.[Medline]
  17. Baggiolini M., Clark-Lewis I. Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett 1992;307:97-101.[Medline]
  18. Ozmen J., Bobryshev Y.V., Lord R.S. CD40 co-stimulatory molecule expression by dendritic cells in primary atherosclerotic lesions in carotid arteries and in stenotic saphenous vein coronary artery grafts. Cardiovasc Surg 2001;9:329-333.[Medline]
  19. Jabs J, Theissing E, Nitschke M, et al. Local generation of C-reactive protein in diseased coronary artery, venous bypass grafts and normal vascular tissue. Circulation 2003;108:1428–37
  20. Cox J.L., Chiasson D.A., Gotlieb A.I. Stranger in a strange land: the pathogenesis of saphenous vein graft stenosis with emphasis on structural and functional differences between veins and arteries. Prog Cardiovasc Dis 1991;34:45-68.[Medline]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. Xing, W. Feng, A. P. Miller, N. M. Weathington, Y.-F. Chen, L. Novak, J. E. Blalock, and S. Oparil
Estrogen modulates TNF-{alpha}-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-beta activation
Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2607 - H2612.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
R. N. Mitchell and P. Libby
Vascular Remodeling in Transplant Vasculopathy
Circ. Res., April 13, 2007; 100(7): 967 - 978.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
A. Schepers, M.R. de Vries, C.J. van Leuven, J.M. Grimbergen, V.M. Holers, M.R. Daha, J.H. van Bockel, and P.H.A. Quax
Inhibition of Complement Component C3 Reduces Vein Graft Atherosclerosis in Apolipoprotein E3-Leiden Transgenic Mice
Circulation, December 19, 2006; 114(25): 2831 - 2838.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A. Schepers, D. Eefting, P.I. Bonta, J.M. Grimbergen, M.R. de Vries, V. van Weel, C.J. de Vries, K. Egashira, J.H. van Bockel, and P.H.A. Quax
Anti-MCP-1 Gene Therapy Inhibits Vascular Smooth Muscle Cells Proliferation and Attenuates Vein Graft Thickening Both In Vitro and In Vivo
Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 2063 - 2069.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
T. Walker, H. P. Wendel, L. Tetzloff, O. Heidenreich, and G. Ziemer
Suppression of ICAM-1 in human venous endothelial cells by small interfering RNAs
Eur. J. Cardiothorac. Surg., December 1, 2005; 28(6): 816 - 820.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Z. Wang, P. J. Rao, M. R. Castresana, and W. H. Newman
TNF-{alpha} induces proliferation or apoptosis in human saphenous vein smooth muscle cells depending on phenotype
Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H293 - H301.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Claus Bartels
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Christiansen, J. F.
Right arrow Articles by Bartels, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Christiansen, J. F.
Right arrow Articles by Bartels, C.
Related Collections
Right arrow Coronary disease

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS