Atherosclerosis inflammation and

Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005 352 1 685-1695. 

Bloomgarden ZT. Inflammation, atherosclerosis, and aspects of insulin action. Diabetes Care 2005 28 2312-2319. 

An interesting link between inflammation, atherosclerosis and NOS has been recently described [60]. In this study, the stimulation of iNOS through endothelin resulted in an increased production of NO, along with a concurrent suppression of the expression of vascular cell adhesion molecule-1 (VCAM-1). It is well known that a hallmark of inflammation is the adhesion of leukocytes to post-capillary venular endothelium and the consequent infiltration of leukocytes into the tissue interstitium. NO, by modulating cytokine-induced ECAM expression through the regulatory factor kB, may here act as antiinflammatory, keeping under control the very basic mechanisms of the atherosclerotic lesion. 

Arachidonic acid lipoxygenases are involved in the synthesis of biomodulators which are strictly related to various diseases allergy, inflammation, atherosclerosis and cancer [77]. 5-Lipoxygenase catalyzes the first step of reactions leading to 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriens responsible for inflammatory and allergic responses. 12-Lipoxygenase catalyzes the formation of 12-HETE, involved in atherosclerosis and tumor metastasis [76]. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

Arnaud C, Veillard NR, Mach F. Cholesterol-independent effects of statins in inflammation, immunomodulation and atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord. 2005 5 127-134. 

Besides 12-LOX in platelets, the 5-LOX isoforms are constitutive in neutrophils. Evidences indicate that LOXs are involved in inflammation diseases and in atherosclerosis. 5-LOX is the enzyme that catalyzes the formation of leukotrienes with potential role for leukocytes and platelets interaction and inflammation. After platelet and leukocyte stimulation, products of both COX-1 and 5-LOX pathways increase. COX-1 activity derivatives increase the vascular permeability mediated by prostaglandins and produce platelet aggregation mediated by TXA2. The product of the lipoxygenase pathway, 5-oxo-6,8,1 1,14-eicosatetraenoic acid (5-Oxo-ETE), induces leukocyte chemotaxis and inflammation. 5-Oxo-ETE is formed by the oxidation of 5S-hydroxy-ETE (5-HETE) by 5-hydroxyeicosanoid dehydrogenase (5-HEDH), a microsomal enzyme found in leukocytes and platelets (42). 

Plasma and urine samples from atherosclerotic and control rats were comparatively analyzed by ultrafast liquid chromatography coupled with ion trap-time-of-flight (IT-TOF) MS (UFLC-IT/TOF-MS) (16). They identified 12 metabolites in rat plasma and 8 metabolites in rat urine as potential biomarkers. Concentrations of leucine, phenylalanine, tryptophan, acetylcar-nitine, butyrylcamitine, propionylcamitine, and spermine in plasma and 3-0-methyl-dopa, ethyl /V2-acety I -1. -argininate, leucylproline, glucuronate, A(6)-(A-threonylcarbonyl)-adenosine, and methyl-hippuric acid in urine were decreased in atherosclerosis rats ursodeoxycholic acid, chenodeoxycholic acid, LPC (06 0), LPC (08 0), and LPC (08 1) in plasma and hippuric acid in urine were increased in atherosclerosis rats. The altered metabolites demonstrated abnormal metabolism of phenylalanine, tryptophan, bile acids, and amino acids. Lysophosphatidylcholine (LPC) plays an important role in inflammation and cell proliferation, which shows a relationship between LPC in the progress of atherosclerosis and other inflammatory diseases. 

Angiotensin II is an octapeptide, which was initially described as a potent vasoconstrictor agent. However, its functions have since been expanded to include regulation of cell growth, inflammation, electrolyte and water balance, hormone secretion, sympathetic nervous system activity, differentiation, and apoptosis. The discovery that it is produced both systemically and locally was instrumental in establishing a pivotal role for the peptide in several disease states, including hypertension, coronary heart disease, myocarditis, congestive heart failure, atherosclerosis, and nephrosclerosis. 

Casserly 1, Topol E (2004) Convergence of atherosclerosis and Alzheimer s disease inflammation, cholesterol, and misfolded proteins. Lancet 363 1139-1146... 

Even though the mortality from coronary heart disease has declined recently, atherosclerosis and related vascular disorders still are the leading cause of death in the Western world. The etiology of this disease is multifactorial, with hyperlipidemia, smoking, diabetes mellitus, hypertension, and obesity being well-established risk factors for the development of atherosclerosis. Dietary fat affects plasma lipids, lipoproteins, and vascular inflammation and, thus, is linked to atherosclerosis. 

These changing concepts of the role of the immune system and inflammation in shoke and cerebrovascular disease have led to searches for new treatment and prevention shategies. This chapter will review the current state of knowledge about inflammation and the immune system in shoke and atherosclerosis and discuss potential therapeutic shategies. 

Abstract Inflammation induces oxidative stress, lipid and protein oxidation and modifies redox equilibrium. At the whole body level, inflammation and oxidative stress contribute to the pathogenesis of many human diseases including atherosclerosis, and related cardiovascular diseases, leading cause of morbidity and mortality in Western countries. 

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. 

Chronic inflammation is an important component in the development and progression of atherosclerosis, and numerous epidemiological studies have demonstrated, that increased serum CRP concentrations are positively associated with a risk of future coronary events, such as coronary artery disease, cerebrovascular disease, or peripheral arterial disease/ " It has also been shown to be predictive of future events in patients with acute coronary syndromes and in patients with stable angina and coronary artery stents. 

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