Autoimmune atherosclerosis

Increased levels of ROS due to oxidative stress have been consistently found in cardiovascular diseases as atherosclerosis or hypertension [18]. There is certain evidence that the free radicals involved in Parkinson s disease are mainly due to the production of increased levels of free radicals during oxidative metabolism of dopamine [19]. Oxidative stress, manifested by protein oxidation and lipid peroxidation (LP), among other alterations, is a characteristic of Alzheimer s disease [20] and in the pathogenesis of diabetes related complications. Treatment with antioxidants seemed to be a promising therapeutic option for these diseases [21], The inflammatory nature of rheumatoid arthritis implies that a state of oxidative stress may also exist in this disease [22,23]. Also, free radicals have a certain role in Huntington s disease [24,25], age related degeneration [26], and some autoimmune disorders [27],... 

Acyl urea derivatives, (I) and (II), prepared by Laborde (3,4), respectively, were effective as MCP-1 antagonists and used in the treatment of chronic or acute inflammatory or autoimmune diseases associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, and atherosclerosis. 

The complex mechanisms underlying inflammation control and its implication in various pathologies have been delineated in this overview. The full comprehension of these mechanisms is necessary to indicate a path for experimenting new treatments for the control of inflammation. The challenge being that of controlling chronic inflammatory processes, at the basis of diseases such as atherosclerosis, neurodegenerative and autoimmune diseases. 

CKs have important roles in a large diversity of human pathological conditions, namely in HIV infection transplant rejection rheumatic, allergic, and autoimmune diseases cancer atherosclerosis and general immunoinflammatory processes (systemic, or related with central nervous system), and are expected as promising targets for new molecular therapies. ... 

The focus of this chapter is on those diseases that are generally accepted to be autoimmune diseases, but descriptive information about some of the other common, potential autoimmune diseases is also included. Diseases that are only recently postulated to be autoimmune (e.g. atherosclerosis) will be mentioned only briefly at the end of this chapter. The respective autoimmune diseases will be discussed in alphabetical order. The topics discussed include... 

Atherosclerosis is a chronic inflammation of the arterial vessel wall resulting in plaque formation that eventually may cause cardiovascular events, such as myocardial infarction or cerebral vascular accidents. The presence of autoimmune components in atherosclerosis is well established. Autoantibodies to heat-shock proteins and oxidized low-density lipoproteins (oxLDL) are prevalent in the circulation of patients with atherosclerosis, but the role of these autoantibodies is debated. While anti-oxLDL IgG antibodies may facilitate uptake of oxLDL by foam cells in the lesions, natural IgM antibodies directed to oxLDL may even protect from atherosclerosis. Atherosclerotic plaques also contain some T cells that are considered to be autoreactive, although the respective autoantigens have not yet been identified. These T cells are probably not involved in the plaque formation as such, but they may cause plaque instability, rupture, and subsequent clinical events. 

Atherosclerosis. A type of arteriosclerosis that is characterized by atheroma formation. It is a multifactorial process leading to the accumulation of lipids within the vessel wall, associated with mononuclear cell infiltration and smooth muscle proliferation. Autoimmune-mediated inflammation may play an important role in accelerated atherosclerosis in autoimmune rheumatic diseases. 

Associations of several autoimmune diseases with atherosclerosis have been observed and a role for LDL oxidation especially in systemic lupus erythematosus (SLE) has been suggested (Frostegard et al. 2005 Hayem et al. 2001 Svenungsson et al. 2001). OxLDL forms immune complexes with p2GPI, which can be detected in the plasma of patients. OxLDL/p2GPI complexes have been demonstrated in patients with syphilis, infectious endocarditis, diabetes melli-tus, antiphospholipid syndrome and chronic nephritis, indicating that oxidation of LDL and the formation of complexes with p2GPI is not restricted to SLE. It is hypothesized that these autoantibodies accelerate the development of atherosclerosis in autoimmune patients. 

Insufficient apoptosis Cancer, autoimmunity, restenosis, persistent infections, atherosclerosis, metabolic disorders. 

Based on their broad range of fimctions, the chemokines are easily deduced to be important players in diseases characterized by inflammation and cell infiltration, such as asthma, atherosclerosis, rheumatoid arthritis, multiple sclerosis, colitis, Crohn s disease, experimental autoimmune encephalomyelitis (EAE), and psoriasis, among others (8). Finally, CXCR4 and CCR5 are the two main coreceptors for HIV-1 infection (9)., some chemokine receptors also participate in tumor metastasis (7) and transplant rejection (10). 

---