Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis

Abstract

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.

Atherosclerosis in Autoimmune Rheumatic Diseases—Mechanisms and Clinical Findings

“…They appear in the arterial intima as early as in 1-year-old children in lesions called "fatty streaks" [8]. Cytotoxic CD8+ T cells also take present in atheromatous lesions, but are less abundant [8].…”

“…Immunohistologic observations revealed that the primary cells to appear in the arterial intima in future atherosclerosis sites are lymphoid cells [8]. T cells are abundant in the atherosclerotic plaques, and TH1 lymphocytes with their pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2) dominating over TH2 lymphocytes, releasing anti-inflammatory mediators such as IL-4, IL-5, and IL-10 [8].…”

“…T cells are abundant in the atherosclerotic plaques, and TH1 lymphocytes with their pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2) dominating over TH2 lymphocytes, releasing anti-inflammatory mediators such as IL-4, IL-5, and IL-10 [8]. They appear in the arterial intima as early as in 1-year-old children in lesions called "fatty streaks" [8]. Cytotoxic CD8+ T cells also take present in atheromatous lesions, but are less abundant [8].…”

“…The nature of atherosclerosis and cardiovascular disease was considered degenerative, and cardiovascular morbidity was believed to be attributed to "traditional" risk factors, such as high blood pressure, cigarette smoking, hypercholesterolemia, diabetes mellitus, obesity, left ventricular hypertrophy, family history, and estrogen replacement therapy [7]; however, growing evidences show that atherosclerosis cannot be fully explained by these traditional factors alone [8], and recent data support the assumption that atherosclerosis is an inflammatory autoimmune disease [4].…”

Local and Systemic Cellular Immunity in Early Renal Artery Atherosclerosis

“…Whether the described features are linked to an autoimmune response remains to be elucidated (36,37). In this respect, the increase CD4/CD8 ratio may resemble the ratio of other autoimmune disorders such as multiple sclerosis (38).…”