Angiogenesis and its potential role in the growth and proliferation of pathogens

Brownyn Lok a; Amin Malik Shah Abdul Majid a; b; Aman Shah Abdul Majid c

doi:10.25163/angiotherapy.11000121421300417

Integrative Biomedical Research

Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN 3068-6326

463

Citations

1.8m

Views

749

Articles

Submit

Volume 1 Number 1 2017

REVIEWS (Open Access)

Next Contents Vol 1 (1)

Angiogenesis and its potential role in the growth and proliferation of pathogens

Abstract Pathogens and Angiogenesis Angiogenesis Induced by Pathogenic Infections Angiogenesis Induced by Helicobacter pylori Infections Angiogenesis Induced by Mycobacterium tuberculosis Infections Angiogenesis Induced by Hepatitis Virus Infections Angiogenesis Induced by Kaposi’s Sarcoma-Associated Herpesvirus Infections Angiogenesis Induced by Orf Virus Infections Conclusion Acknowledgment Author Contribution References

Brownyn Lok ^a*, Amin Malik Shah Abdul Majid^{a, b}, Aman Shah Abdul Majid ^c

+ Author Affiliations

Journal of Angiotherapy 1 (1) 001-011 https://doi.org/10.25163/angiotherapy.11000121421300417

Submitted: 16 April 2017 Revised: 16 April 2017 Published: 16 April 2017

Abstract

Angiogenesis is an important physiological process by which new blood vessels form from pre-existing vessels. Other than being an important physiological process in embryo development, wound healing, and in response to ovulation, it also contributes to the pathology of a number of diseases. Several pathogens, including bacteria, mycobacteria, and viruses, induce angiogenesis during their infection and their pathogenesis within the human body. The excessive angiogenesis induced by the infection of these pathogens usually contributes to the seriousness of the disease. Several bacteria of the Bartonella genus induce angiogenesis during their infection of the human body, as well as Helicobacter pylori and Mycobacterium tuberculosis. Viruses such as the hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi’s sarcoma-associated herpesvirus (KSHV), and orf virus also triggers angiogenesis during their infection. The principal mode of angiogenesis activation is via the stimulation of inflammatory mediators that lead to the increase of VEGF, which is the primary signalling molecule for angiogenesis activation. An increased level of VEGF in the plasma is common in a number of pathogen-induced diseases. The state of hypoxia that resulted from infections activates HIF-1, a transcription factor for VEGF expression. Other important angiogenesis mediators that were activated during pathogenesis include cytokines like IL-6 and -8, angiogenins, as well as the matrix metalloproteinases (MMPs). Hence, targeting angiogenesis may have a potential therapeutic value in treating or managing pathogen infection.

References

Abe, Y., Nakamura, M., Oshika, Y., Hatanaka, H., Tokunaga, T., Ohkubo, Y., . . . Fujino, T. (2001). Serum Levels of Vascular Endothelial Growth Factor and Cavity Formation in Active Pulmonary Tuberculosis. Respiration, 68(5), 496-500.

Adair, T. H., & Montani, J.-P. (2010a). Angiogenesis. Paper presented at the Colloquium Series on Integrated Systems Physiology: From Molecule to Function.

Adair, T. H., & Montani, J.-P. (2010b). Overview of Angiogenesis.

Anderson, B. E., & Neuman, M. A. (1997). Bartonella spp. as Emerging Human Pathogens. Clinical Microbiology Reviews, 10(2), 203-219.

Anderson, D. M., Anderson, L. E., & Glanze, W. D. (2002). Mosby's Medical Dictionary: Mosby St. Louis, MO.

Andreasen, P. A., Kjoller, L., Christensen, L., & Duffy, M. J. (1997). The Urokinase-Type Plasminogen Activator System in Cancer Metastasis: A Review. International Journal of Cancer, 72(1), 1-22.

Aoki, Y., Jaffe, E. S., Chang, Y., Jones, K., Teruya-Feldstein, J., Moore, P. S., & Tosato, G. (1999). Angiogenesis and Hematopoiesis Induced by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Interleukin-6. Blood, 93, 4034-4043.

Biyik Ozkaya, D., Taskin, B., Tas, B., Asiran Serdar, Z., Demirkesen, C., Su, O., & Onsun, N. (2014). Poxvirus-Induced Angiogenesis After a Thermal Burn. The Journal of Dermatology, 41(9), 830-833.

Bos, R., Zhong, H., Hanrahan, C. F., Mommers, E. C., Semenza, G. L., Pinedo, H. M., . . . van der Wall, E. (2001). Levels of Hypoxia-Inducible Factor-1α During Breast Carcinogenesis. Journal of the National Cancer Institute, 93(4), 309-314.

Boshoff, C., & Weiss, R. (2002). AIDS-Related Malignancies. Nature Reviews Cancer, 2(5), 373-382.

Cerimele, F., Brown, L. F., Bravo, F., Ihler, G. M., Kouadio, P., & Arbiser, J. L. (2003). Infectious Angiogenesis: Bartonella bacilliformis Infection Results in Endothelial Production of Angiopoetin-2 and Epidermal Production of Vascular Endothelial Growth Factor. The American Journal of Pathology, 163(4), 1321-1327.

Cesarman, E., Chang, Y., Moore, P. S., Said, J. W., & Knowles, D. M. (1995). Kaposi's Sarcoma–Associated Herpesvirus-Like DNA Sequences in AIDS-Related Body-Cavity–Based Lymphomas. New England Journal of Medicine, 332(18), 1186-1191.

Chang, J. C., Wysocki, A., Tchou-Wong, K.-M., Moskowitz, N., Zhang, Y., & Rom, W. (1996). Effect of Mycobacterium tuberculosis and Its Components on Macrophages and the Release of Matrix Metalloproteinases. Thorax, 51(3), 306-311.

Chang, Y.-J., Wu, M.-S., Lin, J.-T., & Chen, C.-C. (2005). Helicobacter pylori-Induced Invasion and Angiogenesis of Gastric Cells is Mediated by Cyclooxygenase-2 Induction through TLR2/TLR9 and Promoter Regulation. The Journal of Immunology, 175(12), 8242-8252.

Cheng, A. S., Chan, H. L., Leung, W. K., To, K. F., Go, M. Y., Chan, J. Y., . . . Sung, J. J. (2004). Expression of HBx and COX-2 in Chronic Hepatitis B, Cirrhosis and Hepatocellular Carcinoma: Implication of HBx in Upregulation of COX-2. Modern Pathology, 17(10), 1169-1179.

Chung, T.-W., Lee, Y.-C., & Kim, C.-H. (2004). Hepatitis B Viral HBx Induces Matrix Metalloproteinase-9 Gene Expression through Activation of ERK and PI-3K/AKT Pathways: Involvement of Invasive Potential. The FASEB journal, 18(10), 1123-1125.

Cohen, T., Nahari, D., Cerem, L. W., Neufeld, G., & Levi, B.-Z. (1996). Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor. Journal of Biological Chemistry, 271(2), 736-741.

Conway, E. M., Collen, D., & Carmeliet, P. (2001). Molecular Mechanisms of Blood Vessel Growth. Cardiovascular Research, 49(3), 507-521.

Cornali, E., Zietz, C., Benelli, R., Weninger, W., Masiello, L., Breier, G., . . . Stürzl, M. (1996). Vascular Endothelial Growth Factor Regulates Angiogenesis and Vascular Permeability in Kaposi's Sarcoma. The American Journal of Pathology, 149(6), 1851.

Crawford, T. N., Alfaro, I., Kerrison, J. B., & Jablon, E. P. (2009). Diabetic Retinopathy and Angiogenesis. Current Diabetes Reviews, 5(1), 8-13.

Dawes, H., Lapidus, D., Berlin, D., & Meyer, B. (1990). Molecular Mimicry of Human Cytokine and Cytokine Response Pathway Genes by KSHV. Genetics, 124, 91.

Di Bartolo, D. L., Cannon, M., Liu, Y.-F., Renne, R., Chadburn, A., Boshoff, C., & Cesarman, E. (2008). KSHV LANA Inhibits TGF-β Signaling through Epigenetic Silencing of the TGF-β Type II receptor. Blood, 111(9), 4731-4740.

Djonov, V., Baum, O., & Burri, P. H. (2003). Vascular Remodeling by Intussusceptive Angiogenesis. Cell and Tissue Research, 314(1), 107-117.

Dupin, N., Fisher, C., Kellam, P., Ariad, S., Tulliez, M., Franck, N., . . . Escande, J.-P. (1999). Distribution of Human Herpesvirus-8 Latently Infected Cells in Kaposi’s Sarcoma, Multicentric Castleman’s disease, and Primary Effusion Lymphoma. Proceedings of the National Academy of Sciences, 96(8), 4546-4551.

Eklund, L., & Saharinen, P. (2013). Angiopoietin Signaling in the Vasculature. Experimental Cell Research, 319(9), 1271-1280.

Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996). Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia-Inducible Factor 1. Molecular and Cellular Biology, 16(9), 4604-4613.

Foss, H.-d., Araujo, I., Demel, G., Klotzbach, H., Hummel, M., & Stein, H. (1997). Expression of Vascular Endothelial Growth Factor in Lymphomas and Castleman's Disease. The Journal of Pathology, 183(1), 44-50.

Gale, N. W., & Yancopoulos, G. D. (1999). Growth Factors Acting via Endothelial Cell-Specific Receptor Tyrosine Kinases: VEGFs, Angiopoietins, and Ephrins in Vascular Development. Genes & Development, 13(9), 1055-1066.

Gallo, R. C. (1998). The Enigmas of Kaposi's Sarcoma. Science, 282(5395), 1837.

Garcia, F., Wojta, J., Broadley, K., Davidson, J., & Hoover, R. (1990). Bartonella bacilliformis Stimulates Endothelial Cells in vitro and is Angiogenic in vivo. The American Journal of Pathology, 136(5), 1125.

Gong, G., Waris, G., Tanveer, R., & Siddiqui, A. (2001). Human Hepatitis C Virus NS5A Protein Alters Intracellular Calcium Levels, Induces Oxidative Stress, and Activates STAT-3 and NF-κB. Proceedings of the National Academy of Sciences, 98(17), 9599-9604.

Groves, R., Wilson-Jones, E., & MacDonald, D. (1991). Human Orf and Milkers' Nodule: A Clinicopathologic Study. Journal of the American Academy of Dermatology, 25(4), 706-711.

Haimerl, M., Tenter, A., Simon, K., Rommel, M., Hilger, J., & Autenrieth, I. (1999). Seroprevalence of Bartonella henselae in Cats in Germany. Journal of Medical Microbiology, 48(9), 849-856.

Hassan, M., Selimovic, D., Ghozlan, H., & Abdel-kader, O. (2009). Hepatitis C Virus Core Protein Triggers Hepatic Angiogenesis by a Mechanism Including Multiple Pathways. Hepatology, 49(5), 1469-1482.

Hassan, M. M., Li, D., El-Deeb, A. S., Wolff, R. A., Bondy, M. L., Davila, M., & Abbruzzese, J. L. (2008). Association between Hepatitis B Virus and Pancreatic Cancer. Journal of Clinical Oncology, 26(28), 4557-4562.

Holmes, K., Roberts, O. L., Thomas, A. M., & Cross, M. J. (2007). Vascular Endothelial Growth Factor Receptor-2: Structure, Function, Intracellular Signalling and Therapeutic Inhibition. Cellular Signalling, 19(10), 2003-2012.

Ihler, G. M. (1996). Bartonella bacilliformis: Dangerous Pathogen Slowly Emerging from Deep Background. FEMS Microbiology Letters, 144(1), 1-11.

Jackson, L. A., & Spach, D. H. (1996). Emergence of Bartonella quintana Infection Among Homeless Persons. Emerging Infectious Diseases, 2(2), 141.

Karem, K. L., Paddock, C. D., & Regnery, R. L. (2000). Bartonella henselae, B. quintana, and B. bacilliformis: Historical Pathogens of Emerging Significance. Microbes and Infection, 2(10), 1193-1205.

Kempf, V., Schaller, M., Behrendt, S., Volkmann, B., Aepfelbacher, M., Cakman, I., & Autenrieth, I. (2000). Interaction of Bartonella henselae with Endothelial Cells Results in Rapid Bacterial rRNA Synthesis and Replication. Cellular Microbiology, 2(5), 431-441.

Kempf, V. A., Lebiedziejewski, M., Alitalo, K., Wälzlein, J.-H., Ehehalt, U., Fiebig, J., . . . Müller, S. (2005). Activation of Hypoxia-Inducible Factor-1 in Bacillary Angiomatosis. Circulation, 111(8), 1054-1062.

Kempf, V. A., Volkmann, B., Schaller, M., Sander, C. A., Alitalo, K., Riess, T., & Autenrieth, I. B. (2001). Evidence of a Leading Role for VEGF in Bartonella henselae-Induced Endothelial Cell Proliferations. Cellular Microbiology, 3(9), 623-632.

Kim, I., Kim, H. G., Moon, S.-O., Chae, S. W., So, J.-N., Koh, K. N., . . . Koh, G. Y. (2000). Angiopoietin-1 Induces Endothelial Cell Sprouting through the Activation of Focal Adhesion Kinase and Plasmin Secretion. Circulation Research, 86(9), 952-959.

Kimura, H., Weisz, A., Kurashima, Y., Hashimoto, K., Ogura, T., D'Acquisto, F., . . . Esumi, H. (2000). Hypoxia Response Element of the Human Vascular Endothelial Growth Factor Gene Mediates Transcriptional Regulation by Nitric Oxide: Control of Hypoxia-Inducible Factor-1 Activity by Nitric Oxide. Blood, 95(1), 189-197.

Kirby, J. E. (2004). In vitro Model of Bartonella henselae-Induced Angiogenesis. Infection and Immunity, 72(12), 7315-7317.

Kirby, J. E., & Nekorchuk, D. M. (2002). Bartonella-Associated Endothelial Proliferation Depends on Inhibition of Apoptosis. Proceedings of the National Academy of Sciences, 99(7), 4656-4661.

Kiropoulos, T. S., Kostikas, K., & Gourgoulianis, K. I. (2005). Vascular Endothelial Growth Factor Levels in Pleural Fluid and Serum of Patients with Tuberculous Pleural Effusions. CHEST Journal, 128(1), 468-469.

Kitadai, Y., Sasaki, A., Ito, M., Tanaka, S., Oue, N., Yasui, W., . . . Chayama, K. (2003). Helicobacter pylori Infection Influences Expression of Genes Related to Angiogenesis and Invasion in Human Gastric Carcinoma Cells. Biochemical and Biophysical Research Communications, 311(4), 809-814.

Klagsbrun, M., & D'Amore, P. A. (1996). Vascular Endothelial Growth Factor and Its Receptors. Cytokine & Growth Factor Reviews, 7(3), 259-270.

Koehler, J. E., Quinn, F. D., Berger, T. G., LeBoit, P. E., & Tappero, J. W. (1992). Isolation of Rochalimaea Species from Cutaneous and Osseous Lesions of Bacillary Angiomatosis. New England Journal of Medicine, 327(23), 1625-1631.

Krupinski, J., Kaluza, J., Kumar, P., Kumar, S., & Wang, J. M. (1994). Role of Angiogenesis in Patients with Cerebral Ischemic Stroke. Stroke, 25(9), 1794-1798.

Kumar, V., Abbas, A. K., & Aster, J. C. (2012). Robbins Basic Pathology: Elsevier Health Sciences.

Lara-Pezzi, E., Gómez Gaviro, M. V., Gálvez, B. G., Mira, E., Iñiguez, M. Á., Fresno, M., . . . López Cabrera, M. (2002). The Hepatitis B Virus X Protein Promotes Tumor Cell Invasion by Inducing Membrane-Type Matrix Metalloproteinase-1 and Cyclooxygenase-2 Expression. The Journal of Clinical Investigation, 110, 1831-1838.

Lee, S.-W., Lee, Y. M., Bae, S.-K., Murakami, S., Yun, Y., & Kim, K.-W. (2000). Human Hepatitis B virus X Protein is a Possible Mediator of Hypoxia-Induced Angiogenesis in Hepatocarcinogenesis. Biochemical and Biophysical Research Communications, 268(2), 456-461.

Liu, K.-G., Hao, H., Zhao, H., Niu, C.-Y., & Li, L. (2010). Correlation between HBx and VEGF Expressions and Angiogenesis and Metastasis in HBV-Related Hepatocellular Carcinoma Tissue. Journal of Jilin University (Medicine Edition), 36, 372-375.

Liu, L.-p., Liang, H.-f., Chen, X.-p., Zhang, W.-g., Yang, S.-l., Xu, T., & Ren, L. (2010). The Role of NF-κB in Hepatitis B Virus X Protein-Mediated Upregulation of VEGF and MMPs. Cancer Investigation, 28(5), 443-451.

Lobov, I. B., Brooks, P. C., & Lang, R. A. (2002). Angiopoietin-2 Displays VEGF-Dependent Modulation of Capillary Structure and Endothelial Cell Survival in vivo. Proceedings of the National Academy of Sciences, 99(17), 11205-11210.

Lozano, R., Naghavi, M., Foreman, K., Lim, S., Shibuya, K., Aboyans, V., . . . Ahn, S. Y. (2013). Global and Regional Mortality from 235 Causes of Death for 20 Age Groups in 1990 and 2010: A Systematic Analysis for the Global Burden of Disease Study 2010. The Lancet, 380(9859), 2095-2128.

Lyttle, D. J., Fraser, K. M., Fleming, S. B., Mercer, A. A., & Robinson, A. J. (1994). Homologs of Vascular Endothelial Growth Factor are Encoded by the Poxvirus Orf Virus. Journal of Virology, 68(1), 84-92.

Maeno, N., Oda, H., Yoshiie, K., Wahid, M. R., Fujimura, T., & Matayoshi, S. (1999). Live Bartonella henselae Enhances Endothelial Cell Proliferation Without Direct Contact. Microbial Pathogenesis, 27(6), 419-427.

Maeno, N., Yoshiie, K., Matayoshi, S., Fujimura, T., Mao, S., Wahid, M., & Oda, H. (2002). A Heat-Stable Component of Bartonella henselae Upregulates Intercellular Adhesion Molecule-1 Expression on Vascular Endothelial Cells. Scandinavian Journal of Immunology, 55(4), 366-372.

Maguina, C., Garcia, P. J., Gotuzzo, E., Cordero, L., & Spach, D. H. (2001). Bartonellosis (Carrion's disease) in the Modern Era. Clinical Infectious Diseases, 33(6), 772-779.

Martinez, P., Esbrit, P., Rodrigo, A., Alvarez-Arroyo, M., & Martinez, M. (2002). Age-Related Changes in Parathyroid Hormone-Related Protein and Vascular Endothelial Growth Factor in Human Osteoblastic Cells. Osteoporosis International, 13(11), 874-881.

Matsuyama, W., Hashiguchi, T., Matsumuro, K., Iwami, F., Hirotsu, Y., Kawabata, M., . . . Osame, M. (2000). Increased Serum Level of Vascular Endothelial Growth Factor in Pulmonary Tuberculosis. American Journal of Respiratory and Critical Care Medicine, 162(3), 1120-1122.

Matsuyama, W., Hashiguchi, T., Umehara, F., Matsuura, E., Kawabata, M., Arimura, K., . . . Osame, M. (2001). Expression of Vascular Endothelial Growth Factor in Tuberculous Meningitis. Journal of the Neurological Sciences, 186(1), 75-79.

Mayama, S., Cuevas, L. E., Sheldon, J., Omar, O. H., Smith, D. H., Okong, P., . . . Schulz, T. F. (1998). Prevalence and Transmission of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) in Ugandan Children and Adolescents. International Journal of Cancer, 77(6), 817-820.

McCord, A. M., Resto-Ruiz, S. I., & Anderson, B. E. (2006). Autocrine Role for Interleukin-8 in Bartonella henselae-Induced Angiogenesis. Infection and Immunity, 74(9), 5185-5190.

Messerini, L., Novelli, L., & Comin, C. (2004). Microvessel Density and Clinicopathological Characteristics in Hepatitis C Virus and Hepatitis B Virus Related Hepatocellular Carcinoma. Journal of Clinical Pathology, 57(8), 867-871.

Meyer, M., Clauss, M., Lepple-Wienhues, A., Waltenberger, J., Augustin, H. G., Ziche, M., . . . Dehio, C. (1999). A Novel Vascular Endothelial Growth Factor Encoded by Orf Virus, VEGF-E, Mediates Angiogenesis via Signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) Receptor Tyrosine Kinases. The EMBO Journal, 18(2), 363-374.

Montecucco, C., & Rappuoli, R. (2001). Living Dangerously: How Helicobacter pylori Survives in the Human Stomach. Nature Reviews Molecular Cell Biology, 2(6), 457-466.

Moon, E.-J., Jeong, C.-H., Jeong, J.-W., Kim, K. R., Yu, D.-Y., Murakami, S., . . . Kim, K.-W. (2004). Hepatitis B Virus X Protein Induces Angiogenesis by Stabilizing Hypoxia-Inducible Factor-1α. The FASEB journal, 18(2), 382-384.

Mora, X. S., Sanz-Cameno, P., Medina, J., Martin-Vilchez, S., Garcia-Buey, L., Borque, M., & Moreno-Otero, R. (2005). Association between Angiogenesis Soluble Factors and Disease Progression Markers in Chronic Hepatitis C Patients. Revista Espanola de Enfermedades Digestivas, 97(10), 699.

Neipel, F., Albrecht, J.-C., Ensser, A., Huang, Y.-Q., Li, J. J., Friedman-Kien, A. E., & Fleckenstein, B. (1997). Human Herpesvirus 8 Encodes a Homolog of Interleukin-6. Journal of Virology, 71(1), 839-842.

Nunez, O., Fernandez-Martinez, A., Majano, P., Apolinario, A., Gomez-Gonzalo, M., Benedicto, I., . . . Garcia-Monzon, C. (2004). Increased Intrahepatic Cyclooxygenase 2, Matrix Metalloproteinase 2, and Matrix Metalloproteinase 9 Expression is Associated with Progressive Liver Disease in Chronic Hepatitis C Virus Infection: Role of Viral Core and NS5A Proteins. Gut, 53(11), 1665-1672.

Ohl, M. E., & Spach, D. H. (2000). Bartonella quintana and Urban Trench Fever. Clinical Infectious Diseases, 31(1), 131-135.

Ou, D. P., Tao, Y. M., Tang, F. Q., & Yang, L. Y. (2007). The Hepatitis B Virus X Protein Promotes Hepatocellular Carcinoma Metastasis by Upregulation of Matrix Metalloproteinases. International Journal of Cancer, 120(6), 1208-1214.

Paleolog, E. M. (2002). Angiogenesis in Rheumatoid Arthritis. Arthritis Res, 4(Suppl 3), S81-S90.

Parravinci, C., Corbellino, M., Paulli, M., Magrini, U., Lazzarino, M., Moore, P. S., & Chang, Y. (1997). Expression of a Virus-Derived Cytokine, KSHV vIL-6, in HIV-Seronegative Castleman's Disease. The American Journal of Pathology, 151(6), 1517.

Pepper, M. S. (2001). Role of the Matrix Metalloproteinase and Plasminogen Activator–Plasmin Systems in Angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(7), 1104-1117.

Peyssonnaux, C., Datta, V., Cramer, T., Doedens, A., Theodorakis, E. A., Gallo, R. L., . . . Johnson, R. S. (2005). HIF-1α Expression Regulates the Bactericidal Capacity of Phagocytes. Journal of Clinical Investigation, 115(7), 1806.

Qian, L.-W., Xie, J., Ye, F., & Gao, S.-J. (2007). Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases. Journal of Virology, 81(13), 7001-7010.

Resto-Ruiz, S. I., Schmiederer, M., Sweger, D., Newton, C., Klein, T. W., Friedman, H., & Anderson, B. E. (2002). Induction of a Potential Paracrine Angiogenic Loop between Human THP-1 Macrophages and Human Microvascular Endothelial Cells during Bartonella henselae Infection. Infection and Immunity, 70(8), 4564-4570.

Ribatti, D. (2006). Genetic and Epigenetic Mechanisms in the Early Development of the Vascular System. Journal of Anatomy, 208(2), 139-152.

Ridley, M. J., Heather, C., Brown, I., & Willoughby, D. (1983). Experimental Epithelioid Cell Granulomas Tubercle Formation and Immunological Competence: An Ultrastructural Analysis. The Journal of Pathology, 141(2), 97-112.

Ruszczak, Z., da Silva, A. M., & Orfanos, C. (1987). Angioproliferative Changes in Clinically Noninvolved, Perilesional Skin in AIDS-Associated Kaposi’s Sarcoma. Dermatology, 175(6), 270-279.

Sadagopan, S., Sharma-Walia, N., Veettil, M. V., Bottero, V., Levine, R., Vart, R. J., & Chandran, B. (2009). Kaposi's Sarcoma-Associated Herpesvirus Upregulates Angiogenin During Infection of Human Dermal Microvascular Endothelial Cells, Which Induces 45S rRNA Synthesis, Antiapoptosis, Cell Proliferation, Migration, and Angiogenesis. Journal of Virology, 83(7), 3342-3364.

Safai, B., Johnson, K. G., Myskowski, P. L., Koziner, B., Yang, S. Y., Cunningham-Rundles, S., . . . Dupont, B. (1985). The Natural History of Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, 103(5), 744-750.

Saita, N., Fujiwara, N., Yano, I., Soejima, K., & Kobayashi, K. (2000). Trehalose 6, 6′-Dimycolate (Cord Factor) of Mycobacterium tuberculosis Induces Corneal Angiogenesis in Rats. Infection and Immunity, 68(10), 5991-5997.

Sakakibara, S., Pise-Masison, C. A., Brady, J. N., & Tosato, G. (2009). Gene Regulation and Functional Alterations Induced by Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORFK13/vFLIP in Endothelial Cells. Journal of Virology, 83(5), 2140-2153.

Sanz-Cameno, P., Martín-Vílchez, S., Lara-Pezzi, E., Borque, M. J., Salmerón, J., de Rueda, P. M., . . . Moreno-Otero, R. (2006). Hepatitis B Virus Promotes Angiopoietin-2 Expression in Liver Tissue: Role of HBV x Protein. The American Journal of Pathology, 169(4), 1215-1222.

Sasaki, A., Kitadai, Y., Ito, M., Sumii, M., Tanaka, S., Yoshihara, M., . . . Chayama, K. (2003). Helicobacter pylori Infection Influences Tumor Growth of Human Gastric Carcinomas. Scandinavian Journal of Gastroenterology, 38(2), 153-158.

Savory, L. J., Stacker, S. A., Fleming, S. B., Niven, B. E., & Mercer, A. A. (2000). Viral Vascular Endothelial Growth Factor Plays a Critical Role in Orf Virus Infection. Journal of Virology, 74(22), 10699-10706.

Schmid, M. C., Schulein, R., Dehio, M., Denecker, G., Carena, I., & Dehio, C. (2004). The VirB Type IV Secretion System of Bartonella henselae Mediates Invasion, Proinflammatory Activation and Antiapoptotic Protection of Endothelial Cells. Molecular Microbiology, 52(1), 81-92.

Schwalbe, M., Ohlenschläger, O., Marchanka, A., Ramachandran, R., Häfner, S., Heise, T., & Görlach, M. (2008). Solution Structure of Stem-Loop α of the Hepatitis B Virus Post-Transcriptional Regulatory Element. Nucleic Acids Research, 36(5), 1681-1689.

Semenza, G. L. (2001). HIF-1 and Mechanisms of Hypoxia Sensing. Current Opinion in Cell Biology, 13(2), 167-171.

Senger, D. R. (1996). Molecular Framework for Angiogenesis: A Complex Web of Interactions Between Extravasated Plasma Proteins and Endothelial Cell Proteins Induced by Angiogenic Cytokines. The American Journal of Pathology, 149(1), 1.

Sharma-Walia, N., Paul, A. G., Bottero, V., Sadagopan, S., Veettil, M. V., Kerur, N., & Chandran, B. (2010). Kaposi’s Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell survival and Invasion. PLoS Pathog, 6(2), e1000777.

Shelby, B. D., LaMarca, H. L., McFerrin, H. E., Nelson, A. B., Lasky, J. A., Sun, G., . . . Sullivan, D. E. (2007). Kaposi’s Sarcoma Associated Herpesvirus G-Protein Coupled Receptor Activation of Cyclooxygenase-2 in Vascular Endothelial Cells. Virol J, 4, 87.

Struijker, B. H. (1998). Arteriolar and capillary remodelling in hypertension. Drugs, 59, 37-40.

Vart, R. J., Nikitenko, L. L., Lagos, D., Trotter, M. W., Cannon, M., Bourboulia, D., . . . Boshoff, C. (2007). Kaposi's Sarcoma–Associated Herpesvirus-Encoded Interleukin-6 and G-Protein–Coupled Receptor Regulate Angiopoietin-2 Expression in Lymphatic Endothelial Cells. Cancer Research, 67(9), 4042-4051.

Verma, A., Davis, G. E., & Ihler, G. M. (2001). Formation of Stress Fibres in Human Endothelial Cells Infected with Bartonella bacilliformis is Associated with Altered Morphology, Impaired Migration and Defects in Cell Morphogenesis. Cellular Microbiology, 3(3), 169-180.

Vieira, J., O'Hearn, P., Kimball, L., Chandran, B., & Corey, L. (2001). Activation of Kaposi's Sarcoma-Associated Hepesvirus (Hman Hrpesvirus 8) Lytic Replication by Human Cytomegalovirus. Journal of Virology, 75(3), 1378-1386.