Atherosclerosis inflammation

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]. 

LDL, Low-density lipoprotein HDL, high-density lipoprotein CKD, chronic kidney disease MIA, malnutrition inflammation atherosclerosis. 

Nuclear hormone receptor signaling PPAR, RAR, RXR, Progesterone receptor (PR), Androgen receptor (AR), Estrogen receptor (ER), LXR-a, FXR Lipid metabolism. Inflammation, Atherosclerosis, Diabetes, Cancer, Alzheimer s... 

Bacquer, D.D., Clays, E., Delanghe, J., and Backer, D.G. 2006. Epidemiological evidence for an association between habitual tea consumption and markers of chronic inflammation . Atherosclerosis, 7S9 428-35. 

Current evidence suggests that PPAR activation may limit inflammation and hence atherosclerosis. Both PPAR-a and PPAR-y can reduce T-cell activation, as shown by decreased production of EFN-y. PPAR-a agonists also rqness endothelial VCAM-1 expression and inhibit the inflammatory activation of vascular SMCs, while PPAR-y agonists repress endothelial chemokine expression and decrease macrophage MMP production. 

Our new appreciation of the role of inflammation in atherosclerosis shows the way for translation of these novel biological insights to clinical practice, for example by aiding the identification of individuals at risk of adverse cardiovascular events [5]. In this context, inflammatory biomarkers such as CRP merit rigorous consideration for inclusion in risk assessment strategies. In addition, these scientific advances provide a framework... 

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

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. 

A recent patent application from Roche [352] described a 2-amino-benzothiazole series. Roche claimed that compound (605) exhibited an IC50 value of 0.73 uM at CBi, and showed in excess of 10-fold selectivity over the CB2 receptor. The compounds were described as being of potential use in the treatment of a range of diseases, including CNS and psychiatric disorders, type-2 diabetes, gastrointestinal diseases, cardiovascular disorders, infertility disorders, inflammation, cancer, atherosclerosis, cerebral vascular incidents and cranial trauma. 

Prevent or inhibit inflammation by lowering C-reactive protein and other inflammatory mediators thought to be involved in atherosclerosis. 

Atherosclerosis A disease process of the arteries involving fatty plaque formation and inflammation in the vascular wall. 

Key Words Atherosclerosis chemokine chemokine receptor inflammation animal model CCR2 MCP-1 CX3CR1 fractalkine. 

This review reports the more recent evidence for the ability of P-carotene and other carotenoids to modulate cell signaling related to cell growth and implicated in a lot of pathological events, including cancer, inflammation, and atherosclerosis by both redox and non-redox mechanisms. 

Fruchart JC, Duriez P, Staels B. Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol 1999 10 245-257. 

Leon, M. and Zuckerman, S. 2005. Gamma interferon a central mediator in atherosclerosis. Inflammation Research 54(10), 395-411. 

---