Department of Microbiology and Immunology
Gabriel Virella, MD, PhD
1967 M.D., University of Lisbon
1974 Ph.D., University of Lisbon
My current research is focused on the investigation of the role of autoimmune and inflammatory processes in the pathogenesis of human atherosclerosis. We have established unique protocols, now patented, for the isolation and characterization of human antibodies and modified lipoproteins from circulating antigen-antibody complexes formed spontaneously in humans, defined the lipoprotein modification involved in autoimmune reactions in humans, and studies the biological properties of antigen-antibody complexes prepared with human modified LDL and human purified antibodies to modified LDL. The sum of the data generated in collaboration with Dr. Maria Lopes-Virella supports a pathogenic role for the autoimmune response to modified lipoproteins. Currently we are investigating parameters that may have a modulatory effect on the consequences of autoantibody formation against modified LDL, such as the ratio of IgG vs. IgM antibodies and we have demonstrated that the chemical nature of the modified LDL isolated from immune complexes modulates the pathogenic effect of LDL immune complexes in the development of atherosclerosis.
Recent Publications | Additional Publications
Fu D1, Yu JY, Wu M, Du M, Chen Y, Abdel-Samie SA, Li Y, Chen J, Boulton ME, Ma JX, Lopes-Virella MF, Virella G, and Lyons TJ. Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes. J Lipid Res 55:860-9, 2014. doi: 10.1194/jlr.M045401.
Virella G and Lopes-Virella MF. The role of the immune system in the pathogenesis of diabetic complications. Front Endocrinol (Lausanne) 5:126, 2014. doi: 10.3389/fendo.2014.00126. PMID: 25126086.
Virella G, Colglazier J, Chassereau C, and Lopes-Virella MF. Immunoassay of modified forms of human low density lipoprotein in isolated circulating immune complexes. Journal of Immunoassay and Immunochemistry 34:61-74, 2013.
Maria F. Lopes-Virella and G. Virella. The role of immunity and inflammation in the development of diabetic complications. Diabetology International 4:1-8, 2013.
Lopes-Virella MF and Virella G. Pathogenic role of modified LDL antibodies and immune complexes in atherosclerosis. J Atheroscler Thromb 20:743-54, 2013.
Hunt KJ, Baker N, Cleary P, Backlund JY, Lyons T, Jenkins A, Virella G, Lopes-Virella MF, and DCCT/EDIC Research Group. Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes. Atherosclerosis 231:315-22, 2013.
Lopes-Virella, MF, Carter RE, Baker NL, Lachin J, Virella G, and DCCT Research Group. High levels of oxidized LDL in circulating immune complexes are associated with increased odds to develop abnormal albuminuria in type 1 diabetes. Nephrology Dialysis Transplantation 27:1416-1423, 2012.
Truman JP, Al Gadban MM, Smith KJ, Jenkins RW, Mayroo N, Virella G, Lopes-Virella MF, Bielawska A, Hannun YA, and Hammad SM. Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized LDL and oxidized LDL immune complexes: role in phagocytosis and cytokine release. Immunology 136: 30-45, 2012
Virella G, Lopes-Virella MF. The pathogenic role of the adaptive immune response to modified LDL in diabetes. Front Endocrinol (Lausanne) 3:76, 2012.
Lopes-Virella MF, Baker N, Hunt K, Lyons T, Jenkins A, Virella G, and DCCT/EDIC study group. The concentration of AGE-modified LDL and oxidized LDL in circulating immune complexes is associated with progression of retinopathy in type 1 diabetes. Diabetes Care 35:1333-1340, 2012.
Lopes-Virella MF, Baker N, Hunt K, Moritz T, and Virella, G. and the VADT Group of Investigators. The levels of MDA - LDL in circulating immune complexes predict myocardial infarction in the VADT study. Atherosclerosis 224:526-531, 2012.
Abdelsamie SA, Li Y, Huang Y, Lee MH, Klein RL, Virella G, and Lopes-Virella MF. Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III. Clinical Immunology 139:258-66, 2011.
Klein RL, Carter RE, Jenkins AJ, Lyons TJ, Baker NL, Gilbert GE, Virella G, Lopes-Virella MF, the DCCT/EDIC Research Group. LDL-containing immune complexes in the DCCT/EDIC cohort: associations with lipoprotein subclasses. J Diabetes Complications 25:73-82, 2011.
Lopes-Virella MF, Baker NL, Hunt KJ, Lachin J, Nathan D, and Virella G. Oxidized LDL immune complexes and coronary artery calcification in Type 1 diabetes. Atherosclerosis 214:462-467, 2011.
Lopes-Virella MF, Hunt KJ, Baker NL, Lachin J, Nathan DM, Virella G, and the DCCT/EDIC Research Group. Levels of oxidized LDL and advanced glycation end products-modified LDL in circulating immune complexes are strongly associated with increased levels of carotid intima-media thickness and its progression in type 1 diabetes. Diabetes 60:582-589, 2011.
Virella G. Immunology of Cardiovascular Disease: Introduction to a special issue of Clinical Immunology. (Virella, G. and Lopes-Virella, M.F., Editors). Clinical Immunology 134:1-4, 2010.
Lopes-Virella MF and Virella G. Clinical significance of the humoral immune response to modified LDL. Clinical Immunology 134:55-65, 2010.
Smith KJ, Twal WO, Soodavar F, Virella G, Lopes-Virella MF, and Hammad SM. Heat shock protein 70B' (HSP70B') expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. J Biol Chem 285:15985-93, 2010.
Al Gadban MM, Smith KJ, Soodavar F, Piansay C, Chassereau C, Twal WO, Klein RL, Virella G, Lopes-Virella MF, and Hammad SM. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress. PLoS One 5(9), 2010. pii: e12534.