Skip to main content
Erschienen in: Inflammation 4/2012

01.08.2012

Lipopolysaccharide-Induced Proliferation of the Vasa Vasorum in a Rabbit Model of Atherosclerosis as Evaluated by Contrast-Enhanced Ultrasound Imaging and Histology

verfasst von: Jinwei Tian, Sining Hu, Xue Han, Nana Dong, Huai Yu, Yanli Sun, Bo Yu

Erschienen in: Inflammation | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

Whether lipopolysaccharide (LPS) can promote vasa vasorum (VV) proliferation for atherosclerosis in vivo is unclear. Eighteen rabbits with atherosclerosis were randomly assigned into one of three groups of six. Group A received biweekly injections of 10 mL saline after 2 weeks of balloon injury. Groups B and C received biweekly intravenous injections of 3.0 μg LPS in 10 mL saline at weeks 10 and 4, respectively, until study termination. LPS significantly increased the levels of triglycerides and C-reactive protein and decreased the level of high-density lipoprotein cholesterol. Group C had significant larger plaques and more macrophages than group A (p = 0.01 and p < 0.001, respectively). Contrast enhancement ultrasound imaging and histological detection demonstrated that plaques in group C had a significantly higher VV density than that in group A (p = 0.009 and p = 0.002, respectively). In summary, VV proliferation for plaque destabilization can be accelerated by LPS-induced systemic inflammation and changes in lipid profiles.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Raetz, C.R., and C. Whitfield. 2002. Lipopolysaccharide endotoxins. Annual Review of Biochemistry 71: 635–700.PubMedCrossRef Raetz, C.R., and C. Whitfield. 2002. Lipopolysaccharide endotoxins. Annual Review of Biochemistry 71: 635–700.PubMedCrossRef
2.
Zurück zum Zitat Wiedermann, C.J., S. Kiechl, S. Dunzendorfer, P. Schratzberger, G. Egger, F. Oberhollenzer, and J. Willeit. 1999. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck study. Journal of the American College of Cardiology 34: 1975–1981.PubMedCrossRef Wiedermann, C.J., S. Kiechl, S. Dunzendorfer, P. Schratzberger, G. Egger, F. Oberhollenzer, and J. Willeit. 1999. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck study. Journal of the American College of Cardiology 34: 1975–1981.PubMedCrossRef
3.
Zurück zum Zitat Lehr, H.A., T.A. Sagban, C. Ihling, U. Zahringer, K.D. Hungerer, M. Blumrich, K. Reifenberg, and S. Bhakdi. 2001. Immunopathogenesis of atherosclerosis: endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet. Circulation 104: 914–920.PubMedCrossRef Lehr, H.A., T.A. Sagban, C. Ihling, U. Zahringer, K.D. Hungerer, M. Blumrich, K. Reifenberg, and S. Bhakdi. 2001. Immunopathogenesis of atherosclerosis: endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet. Circulation 104: 914–920.PubMedCrossRef
4.
Zurück zum Zitat Engelmann, M.G., C.V. Redl, and S. Nikol. 2004. Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo. Laboratory Investigation 84: 425–432.PubMedCrossRef Engelmann, M.G., C.V. Redl, and S. Nikol. 2004. Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo. Laboratory Investigation 84: 425–432.PubMedCrossRef
5.
Zurück zum Zitat Kim, S.J., J.H. Park, K.H. Kim, W.R. Lee, S. Lee, O.C. Kwon, K.S. Kim, and K.K. Park. 2010. Effect of NF-κB decoy oligodeoxynucleotide on LPS/high-fat diet-induced atherosclerosis in an animal model. Basic & Clinical Pharmacology & Toxicology 107: 925–930.CrossRef Kim, S.J., J.H. Park, K.H. Kim, W.R. Lee, S. Lee, O.C. Kwon, K.S. Kim, and K.K. Park. 2010. Effect of NF-κB decoy oligodeoxynucleotide on LPS/high-fat diet-induced atherosclerosis in an animal model. Basic & Clinical Pharmacology & Toxicology 107: 925–930.CrossRef
6.
Zurück zum Zitat Sluimer, J.C., F.D. Kolodgie, A.P. Bijnens, K. Maxfield, E. Pacheco, B. Kutys, H. Duimel, P.M. Frederik, V.W. van Hinsbergh, R. Virmani, and M.J. Daemen. 2009. Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. Journal of the American College of Cardiology 53: 1517–1527.PubMedCrossRef Sluimer, J.C., F.D. Kolodgie, A.P. Bijnens, K. Maxfield, E. Pacheco, B. Kutys, H. Duimel, P.M. Frederik, V.W. van Hinsbergh, R. Virmani, and M.J. Daemen. 2009. Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. Journal of the American College of Cardiology 53: 1517–1527.PubMedCrossRef
7.
Zurück zum Zitat Koo, T.H., H.O. Jun, S.K. Bae, S.R. Kim, C.P. Moon, S.K. Jeong, W.S. Kim, G.C. Kim, H.O. Jang, I. Yun, K.W. Kim, and M.K. Bae. 2007. Porphyromonas gingivalis, periodontal pathogen, lipopolysaccharide induces angiogenesis via extracellular signal-regulated kinase 1/2 activation in human vascular endothelial cells. Archives of Pharmacal Research 30: 34–42.PubMedCrossRef Koo, T.H., H.O. Jun, S.K. Bae, S.R. Kim, C.P. Moon, S.K. Jeong, W.S. Kim, G.C. Kim, H.O. Jang, I. Yun, K.W. Kim, and M.K. Bae. 2007. Porphyromonas gingivalis, periodontal pathogen, lipopolysaccharide induces angiogenesis via extracellular signal-regulated kinase 1/2 activation in human vascular endothelial cells. Archives of Pharmacal Research 30: 34–42.PubMedCrossRef
8.
Zurück zum Zitat Staub, D., M.B. Patel, A. Tibrewala, D. Ludden, M. Johnson, P. Espinosa, B. Coll, K.A. Jaeger, and S.B. Feinstein. 2010. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke 41: 41–47.PubMedCrossRef Staub, D., M.B. Patel, A. Tibrewala, D. Ludden, M. Johnson, P. Espinosa, B. Coll, K.A. Jaeger, and S.B. Feinstein. 2010. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke 41: 41–47.PubMedCrossRef
9.
Zurück zum Zitat Moguillansky, D., X. Leng, A. Carson, L. Lavery, A. Schwartz, X. Chen, and F.S. Villanueva. 2011. Quantification of plaque neovascularization using contrast ultrasound: a histologic validation. European Heart Journal 32: 646–653.PubMedCrossRef Moguillansky, D., X. Leng, A. Carson, L. Lavery, A. Schwartz, X. Chen, and F.S. Villanueva. 2011. Quantification of plaque neovascularization using contrast ultrasound: a histologic validation. European Heart Journal 32: 646–653.PubMedCrossRef
10.
Zurück zum Zitat Meng, L., B. Lv, S. Zhang, and B. Yv. 2008. in vivo optical coherence tomography of experimental thrombosis in a rabbit carotid model. Heart 94: 777–780.PubMedCrossRef Meng, L., B. Lv, S. Zhang, and B. Yv. 2008. in vivo optical coherence tomography of experimental thrombosis in a rabbit carotid model. Heart 94: 777–780.PubMedCrossRef
11.
Zurück zum Zitat Mattsby-Baltzer, I., A. Jakobsson, J. Sorbo, and K. Norrby. 1994. Endotoxin is angiogenic. International Journal of Experimental Pathology 75: 191–196.PubMed Mattsby-Baltzer, I., A. Jakobsson, J. Sorbo, and K. Norrby. 1994. Endotoxin is angiogenic. International Journal of Experimental Pathology 75: 191–196.PubMed
12.
Zurück zum Zitat Harmey, J.H., C.D. Bucana, W. Lu, A.M. Byrne, S. McDonnell, C. Lynch, D. Bouchier-Hayes, and Z. Dong. 2002. Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. International Journal of Cancer 101: 415–422.CrossRef Harmey, J.H., C.D. Bucana, W. Lu, A.M. Byrne, S. McDonnell, C. Lynch, D. Bouchier-Hayes, and Z. Dong. 2002. Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. International Journal of Cancer 101: 415–422.CrossRef
13.
Zurück zum Zitat Kolodgie, F.D., H.K. Gold, A.P. Burke, D.R. Fowler, H.S. Kruth, D.K. Weber, A. Farb, L.J. Guerrero, M. Hayase, R. Kutys, J. Narula, A.V. Finn, and R. Virmani. 2003. Intraplaque hemorrhage and progression of coronary atheroma. The New England Journal of Medicine 349: 2316–2325.PubMedCrossRef Kolodgie, F.D., H.K. Gold, A.P. Burke, D.R. Fowler, H.S. Kruth, D.K. Weber, A. Farb, L.J. Guerrero, M. Hayase, R. Kutys, J. Narula, A.V. Finn, and R. Virmani. 2003. Intraplaque hemorrhage and progression of coronary atheroma. The New England Journal of Medicine 349: 2316–2325.PubMedCrossRef
14.
Zurück zum Zitat Leibovich, S.J., J.F. Chen, G. Pinhal-Enfield, P.C. Belem, G. Elson, A. Rosania, M. Ramanathan, C. Montesinos, M. Jacobson, M.A. Schwarzschild, J.S. Fink, and B. Cronstein. 2002. Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A (2A) receptor agonists and endotoxin. American Journal of Pathology 160: 2231–2244.PubMedCrossRef Leibovich, S.J., J.F. Chen, G. Pinhal-Enfield, P.C. Belem, G. Elson, A. Rosania, M. Ramanathan, C. Montesinos, M. Jacobson, M.A. Schwarzschild, J.S. Fink, and B. Cronstein. 2002. Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A (2A) receptor agonists and endotoxin. American Journal of Pathology 160: 2231–2244.PubMedCrossRef
15.
Zurück zum Zitat Ramanathan, M., G. Pinhal-Enfield, I. Hao, and S.J. Leibovich. 2007. Synergistic up-regulation of vascular endothelial growth factor (VEGF) expression in macrophages by adenosine A2A receptor agonists and endotoxin involves transcriptional regulation via the hypoxia response element in the VEGF promoter. Molecular Biology of the Cell 18: 14–23.PubMedCrossRef Ramanathan, M., G. Pinhal-Enfield, I. Hao, and S.J. Leibovich. 2007. Synergistic up-regulation of vascular endothelial growth factor (VEGF) expression in macrophages by adenosine A2A receptor agonists and endotoxin involves transcriptional regulation via the hypoxia response element in the VEGF promoter. Molecular Biology of the Cell 18: 14–23.PubMedCrossRef
16.
Zurück zum Zitat Kiriakidis, S., E. Andreakos, C. Monaco, B. Foxwell, M. Feldmann, and E. Paleolog. 2003. VEGF expression in human macrophages is NF-kappaB-dependent: studies using adenoviruses expressing the endogenous NF-kappaB inhibitor IkappaBalpha and a kinase-defective form of the IkappaB kinase 2. Journal of Cell Science 116: 665–674.PubMedCrossRef Kiriakidis, S., E. Andreakos, C. Monaco, B. Foxwell, M. Feldmann, and E. Paleolog. 2003. VEGF expression in human macrophages is NF-kappaB-dependent: studies using adenoviruses expressing the endogenous NF-kappaB inhibitor IkappaBalpha and a kinase-defective form of the IkappaB kinase 2. Journal of Cell Science 116: 665–674.PubMedCrossRef
17.
Zurück zum Zitat Ramanathan, M., A. Giladi, and S.J. Leibovich. 2003. Regulation of vascular endothelial growth factor gene expression in murine macrophages by nitric oxide and hypoxia. Experimental Biology and Medicine (Maywood) 228: 697–705. Ramanathan, M., A. Giladi, and S.J. Leibovich. 2003. Regulation of vascular endothelial growth factor gene expression in murine macrophages by nitric oxide and hypoxia. Experimental Biology and Medicine (Maywood) 228: 697–705.
18.
Zurück zum Zitat Shi, Q., L.A. Cox, J. Glenn, M.E. Tejero, V. Hondara, J.L. Vandeberg, and X.L. Wang. 2010. Molecular pathways mediating differential responses to lipopolysaccharide between human and baboon arterial endothelial cells. Clinical and Experimental Pharmacology and Physiology 37: 178–184.PubMedCrossRef Shi, Q., L.A. Cox, J. Glenn, M.E. Tejero, V. Hondara, J.L. Vandeberg, and X.L. Wang. 2010. Molecular pathways mediating differential responses to lipopolysaccharide between human and baboon arterial endothelial cells. Clinical and Experimental Pharmacology and Physiology 37: 178–184.PubMedCrossRef
19.
Zurück zum Zitat Liu, H.T., W.M. Li, X.Y. Li, Q.S. Xu, Q.S. Liu, X.F. Bai, C. Yu, and Y.G. Du. 2010. Chitosan oligosaccharides inhibit the expression of interleukin-6 in lipopolysaccharide-induced human umbilical vein endothelial cells through p38 and ERK1/2 protein kinases. Basic & Clinical Pharmacology & Toxicology 106: 362–371. Liu, H.T., W.M. Li, X.Y. Li, Q.S. Xu, Q.S. Liu, X.F. Bai, C. Yu, and Y.G. Du. 2010. Chitosan oligosaccharides inhibit the expression of interleukin-6 in lipopolysaccharide-induced human umbilical vein endothelial cells through p38 and ERK1/2 protein kinases. Basic & Clinical Pharmacology & Toxicology 106: 362–371.
20.
Zurück zum Zitat Lin, C.M., H. Chang, Y.H. Chen, S.Y. Li, I.H. Wu, and J.H. Chiu. 2006. Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1. International Immunopharmacology 6: 1690–1698.PubMedCrossRef Lin, C.M., H. Chang, Y.H. Chen, S.Y. Li, I.H. Wu, and J.H. Chiu. 2006. Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1. International Immunopharmacology 6: 1690–1698.PubMedCrossRef
21.
Zurück zum Zitat Lin, C.M., H. Chang, S.Y. Li, I.H. Wu, and J.H. Chiu. 2006. Chrysin inhibits lipopolysaccharide-induced angiogenesis via down-regulation of VEGF/VEGFR-2(KDR) and IL-6/IL-6R pathways. Planta Medica 72: 708–714.PubMedCrossRef Lin, C.M., H. Chang, S.Y. Li, I.H. Wu, and J.H. Chiu. 2006. Chrysin inhibits lipopolysaccharide-induced angiogenesis via down-regulation of VEGF/VEGFR-2(KDR) and IL-6/IL-6R pathways. Planta Medica 72: 708–714.PubMedCrossRef
22.
Zurück zum Zitat Chen, Y., N. Lu, Y. Ling, Y. Gao, L. Wang, Y. Sun, Q. Qi, F. Feng, W. Liu, Q. You, and Q. Guo. 2009. Wogonoside inhibits lipopolysaccharide-induced angiogenesis in vitro and in vivo via toll-like receptor 4 signal transduction. Toxicology 259: 10–17.PubMedCrossRef Chen, Y., N. Lu, Y. Ling, Y. Gao, L. Wang, Y. Sun, Q. Qi, F. Feng, W. Liu, Q. You, and Q. Guo. 2009. Wogonoside inhibits lipopolysaccharide-induced angiogenesis in vitro and in vivo via toll-like receptor 4 signal transduction. Toxicology 259: 10–17.PubMedCrossRef
23.
Zurück zum Zitat Li, H., M.W. Freeman, and P. Libby. 1995. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines. Journal of Clinical Investigation 95: 122–133.PubMedCrossRef Li, H., M.W. Freeman, and P. Libby. 1995. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines. Journal of Clinical Investigation 95: 122–133.PubMedCrossRef
24.
Zurück zum Zitat Ostos, M.A., D. Recalde, M.M. Zakin, and D. Scott-Algara. 2002. Implication of natural killer T cells in atherosclerosis development during a LPS-induced chronic inflammation. FEBS Letters 519: 23–29.PubMedCrossRef Ostos, M.A., D. Recalde, M.M. Zakin, and D. Scott-Algara. 2002. Implication of natural killer T cells in atherosclerosis development during a LPS-induced chronic inflammation. FEBS Letters 519: 23–29.PubMedCrossRef
25.
Zurück zum Zitat Westerterp, M., J.F. Berbee, N.M. Pires, G.J. van Mierlo, R. Kleemann, J.A. Romijn, L.M. Havekes, and P.C. Rensen. 2007. Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice. Circulation 116: 2173–2181.PubMedCrossRef Westerterp, M., J.F. Berbee, N.M. Pires, G.J. van Mierlo, R. Kleemann, J.A. Romijn, L.M. Havekes, and P.C. Rensen. 2007. Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice. Circulation 116: 2173–2181.PubMedCrossRef
26.
Zurück zum Zitat Lin, F.Y., Y.H. Chen, Y.W. Lin, J.S. Tsai, J.W. Chen, H.J. Wang, Y.L. Chen, C.Y. Li, and S.J. Lin. 2006. The role of human antigen R, an RNA-binding protein, in mediating the stabilization of toll-like receptor 4 mRNA induced by endotoxin: a novel mechanism involved in vascular inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology 26: 2622–2629.PubMedCrossRef Lin, F.Y., Y.H. Chen, Y.W. Lin, J.S. Tsai, J.W. Chen, H.J. Wang, Y.L. Chen, C.Y. Li, and S.J. Lin. 2006. The role of human antigen R, an RNA-binding protein, in mediating the stabilization of toll-like receptor 4 mRNA induced by endotoxin: a novel mechanism involved in vascular inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology 26: 2622–2629.PubMedCrossRef
27.
Zurück zum Zitat Feng, X., Y. Zhang, R. Xu, X. Xie, L. Tao, H. Gao, Y. Gao, Z. He, and H. Wang. 2010. Lipopolysaccharide up-regulates the expression of Fcalpha/mu receptor and promotes the binding of oxidized low-density lipoprotein and its IgM antibody complex to activated human macrophages. Atherosclerosis 208: 396–405.PubMedCrossRef Feng, X., Y. Zhang, R. Xu, X. Xie, L. Tao, H. Gao, Y. Gao, Z. He, and H. Wang. 2010. Lipopolysaccharide up-regulates the expression of Fcalpha/mu receptor and promotes the binding of oxidized low-density lipoprotein and its IgM antibody complex to activated human macrophages. Atherosclerosis 208: 396–405.PubMedCrossRef
28.
Zurück zum Zitat Goteiner, D., R.G. Craig, R. Ashmen, M.N. Janal, B. Eskin, and N. Lehrman. 2008. Endotoxin levels are associated with high-density lipoprotein, triglycerides, and troponin in patients with acute coronary syndrome and angina: possible contributions from periodontal sources. Journal of Periodontology 79: 2331–2339.PubMedCrossRef Goteiner, D., R.G. Craig, R. Ashmen, M.N. Janal, B. Eskin, and N. Lehrman. 2008. Endotoxin levels are associated with high-density lipoprotein, triglycerides, and troponin in patients with acute coronary syndrome and angina: possible contributions from periodontal sources. Journal of Periodontology 79: 2331–2339.PubMedCrossRef
29.
Zurück zum Zitat Cue, J.I., J.T. DiPiro, L.J. Brunner, J.E. Doran, M.E. Blankenship, A.R. Mansberger, and M.L. Hawkins. 1994. Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis factor alpha responses to lipopolysaccharide in rabbits. Archives of Surgery 129: 193–197.PubMedCrossRef Cue, J.I., J.T. DiPiro, L.J. Brunner, J.E. Doran, M.E. Blankenship, A.R. Mansberger, and M.L. Hawkins. 1994. Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis factor alpha responses to lipopolysaccharide in rabbits. Archives of Surgery 129: 193–197.PubMedCrossRef
30.
Zurück zum Zitat Skyba, D.M., A.R. Jayaweera, N.C. Goodman, S. Ismail, G. Camarano, and S. Kaul. 1994. Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection. Circulation 90: 1513–1521.PubMedCrossRef Skyba, D.M., A.R. Jayaweera, N.C. Goodman, S. Ismail, G. Camarano, and S. Kaul. 1994. Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection. Circulation 90: 1513–1521.PubMedCrossRef
31.
Zurück zum Zitat Staub, D., A.F. Schinkel, B. Coll, S. Coli, A.F. van der Steen, J.D. Reed, C. Krueger, K.E. Thomenius, D. Adam, E.J. Sijbrands, F.J. ten Cate, and S.B. Feinstein. 2010. Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC. Cardiovascular Imaging 3: 761–771.PubMedCrossRef Staub, D., A.F. Schinkel, B. Coll, S. Coli, A.F. van der Steen, J.D. Reed, C. Krueger, K.E. Thomenius, D. Adam, E.J. Sijbrands, F.J. ten Cate, and S.B. Feinstein. 2010. Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC. Cardiovascular Imaging 3: 761–771.PubMedCrossRef
32.
Zurück zum Zitat Feinstein, S.B. 2006. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. Journal of the American College of Cardiology 48: 236–243.PubMedCrossRef Feinstein, S.B. 2006. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. Journal of the American College of Cardiology 48: 236–243.PubMedCrossRef
Metadaten
Titel
Lipopolysaccharide-Induced Proliferation of the Vasa Vasorum in a Rabbit Model of Atherosclerosis as Evaluated by Contrast-Enhanced Ultrasound Imaging and Histology
verfasst von
Jinwei Tian
Sining Hu
Xue Han
Nana Dong
Huai Yu
Yanli Sun
Bo Yu
Publikationsdatum
01.08.2012
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 4/2012
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-012-9468-z

Weitere Artikel der Ausgabe 4/2012

Inflammation 4/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.