American Diabetes Association Honors Dr. Lopes-Virella

Dr. Maria Lopes-Virella, Professor of Medicine at the Medical University of South Carolina (MUSC), and Physician at the Ralph H. Johnson VA Medical Center was recognized June 24 at the National Meeting of the American Diabetes Association held in Philadelphia for her outstanding contributions to the study of the pathogenesis of diabetes complications.

She delivered the Edwin Bierman Lecture, instituted in 1998, to honor Dr. Bierman's memory. An outstanding investigator in the field of diabetes complications in the latter part of the 20th Century, Dr. Bierman left a great legacy not only from his published work, but also in his past collaborators that have continued his work in some of the nation's premier medical centers. The recipient of the Edwin Bierman Lectureship is chosen annually by a selection committee of the Council on Complications of the American Diabetes Association. Dr. Virella is the second faculty member from MUSC to be honored in successive years. Dr. John Colwell presented last year's Bierman lecture.

Increasing Scope of StudyA Little Background

Dr. Lopes-Virella has been actively engaged in diabetes research in the past two decades. In 1977, soon after she joined Dr. John Colwell's group at the Division of Endocrinology, she was the senior author of the first publication reporting unique lipid abnormalities in poorly controlled diabetics that could explain their predisposition to develop cardiovascular disease. This initial work was followed by a series of reports, which contributed to establishing that lipoproteins from patients with diabetes are altered in a number of ways and that these alterations affect the metabolism of these lipoproteins and increase their atherogenicity by a variety of mechanisms, such as enhancing platelet aggregation. A large part of her work in lipoprotein metabolism was performed after she joined the Ralph H. Johnson VA Medical Center Research Service as a Clinical Investigator.

As her research evolved, Dr. Lopes-Virella focused on the study of autoimmune responses against different types of modified LDL often found in diabetic patients. These autoantibodies are able to react with modified lipoproteins, forming antigen-antibody complexes that are able to trigger a variety of cellular reactions with the potential of initiating or perpetuating the atherosclerotic process. In vitro studies performed in her laboratory demonstrated that antigen-antibody complexes prepared with human lipoproteins and rabbit antibodies are able to reproduce the majority of the cellular reactions that have been proposed to lead to the development of arteriosclerotic lesions. The pathways involved in the transmission of activation signals after the lipoprotein immune complexes interact with membrane receptors on macrophage-like cell lines have been actively investigated by scientists in her group, hoping to open new therapeutic approaches for hyperlipidemia.

Increasing Scope of Study

As an extension of the studies carried out in vitro with model antigen-antibody complexes, Dr. Lopes-Virella's group has conducted significant research looking for correlates in humans. They developed a competitive immunoassay for circulating antibodies against human modified lipoproteins, techniques for the isolation of antibodies to modified lipoproteins, and techniques for the isolation and characterization of lipoprotein-containing immune complexes from patient's serum. The data generated by these techniques have enabled broader studies, some investigating the atherogenic and pro-inflammatory properties of lipoprotein-containing complexes isolated from the serum of diabetics, others testing the same properties using antigen-antibody complexes prepared with human modified lipoproteins and the corresponding human antibodies.

Dr. Lopes-Virella has also examined epidemiological links between antibody formation against modified lipoproteins and macrovascular disease in diabetics. Data generated so far suggest that antigen-antibody complexes containing modified LDL play a pathogenic role in the development of both microvascular complications (retinopathy, nephropathy) and macrovascular disease (coronary artery disease, major vessel atherosclerosis). The characterization of antibodies to oxidized LDL and other forms of modified LDL prevalent in diabetics has shown that the antibodies belong predominantly to the pro-inflammatory isotypes and that the avidity of these antibodies is directly related to their pathogenic potential. The prognostic and therapeutic implications of these findings are subjects of future projects in Dr. Lopes-Virella's laboratory.

Letting Others Know the Results

Dr. Lopes-Virella has published a total of 126 articles and book chapters. She has lectured extensively in the United States and has had continuous federal funding for her research since 1978. Currently, she holds three major research grants, two from the NIH and another from the VA Merit Review Program. Join us in congratulating SELA's President on her stellar accomplishments and this great honor.