Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis

Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed

Natural anticoagulant and fibrinolytic pathways in renal allograft failure.

This is an immunocytochemical study of the relationship between depletion of natural anticoagulant and fibrinolytic pathways and allograft survival following renal transplantation. Patients (n = 44) were classified in three groups according to the length of time between transplantation and allograft failure: group 1 (n = 14) failed within a month of transplantation; group 2 (n = 14) failed between one month and one year after transplantation; and group 3 (n = 16) failed after one year of transplantation. Control biopsies were from donor kidneys (n = 16) prior to transplantation. There were no statistically significant differences in recipient age, gender, donor kidney type (living-related versus cadaver), histocompatibility, and plasma cholesterol, triglycerides, or creatinine concentrations between groups. However, group 1 allografts had a greater depletion of the vascular heparan sulfate proteoglycan-antithrombin III natural anticoagulant pathway than allografts in group 2 or 3 (P < or = 0.05), and this depletion was associated with significantly greater fibrin deposition in group 1 than in either group 2 or 3 (P < or = 0.05). All three groups demonstrated severe depletion of tissue plasminogen activator from arteriolar smooth muscle cells and depressed fibrinolysis as evidenced by increased fibrin/plasmin ratios. However, no significant differences were found for either endothelial thrombomodulin or T cell, neutrophil, or macrophage infiltration between the groups. These data indicate that differences in graft outcome may be determined more by compromised vascular function than by the presence of cellular infiltrates

Antibodies to endothelial cells identify myocardial damage and predict development of coronary artery disease in patients with transplanted hearts

Transplant-induced coronary artery disease is a leading cause of graft failure in cardiac allograft recipients after the first year of transplantation, but there presently is no test to identify patients at high risk for developing the disease. Our research is focused on development of a predictive test to identify patients at high risk of developing the disease