Diabetes atherosclerosis and

NADPH oxidases (NOX), catalyzing the reduction of molecular oxygen to form the superoxide radical anion (02 ) and hydrogen peroxide (H202), are involved in stroke, diabetes, atherosclerosis, and chronic neurodegenerative diseases. GKT136901 is a novel NOX-1/4 inhibitor with potential application in the areas of... 

HDACs play a fundamental role in determining the state of chromatin, and are involved in the modulation of numerous other important proteins. Thus, although the first human HDACs were only identified a decade ago, it is not surprising that these enzymes are already attractive therapeutic targets [8] for a host of diseases including cancer, neurodegenerative disorders, cardiac hypertrophy, inflammation, diabetes, atherosclerosis, and infectious diseases. 

On the basis of the standard presented above, the incidence of obesity is estimated as low before 20, rising sharply after 30, and reaching a maximum in the sixth decade. The incidence of obesity drops after the sixth decade because obese people die younger, and older people spontaneously reduce their food intake. Approximately 30% of the middle-aged American population is obese. In addition to the cosmetic disadvantages, the hazards of obesity are numerous. The incidence of diabetes, atherosclerosis, and hypertension is greater in the obese. The relationship between these diseases and obesity is discussed in other sections of this book. 

As described in the previous section, bile acids have evolved over the last years from regulators of bile acid homeostasis to general metabolic integrators. It is therefore not too surprizing that a number of bile acid-activated signaling pathways have become attractive targets for the treatment of gallstones and other metabolic diseases, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. 

Figure 1-1. Examples ofthe two-way street connecting biochemistry and medicine. Knowledge ofthe biochemical molecules shown in the top part of the diagram has clarified our understanding ofthe diseases shown in the bottom half—and conversely, analyses ofthe diseases shown below have cast light on many areas of biochemistry. Note that sickle cell anemia is a genetic disease and that both atherosclerosis and diabetes mellitus have genetic components.

Factors that predispose an individual to IHD are listed in Table 4—2. Hypertension, diabetes, dyslipidemia, and cigarette smoking are associated with endothelial dysfunction and potentiate atherosclerosis of the coronary arteries. The risk for IHD increases two-fold for every 20 mm Hg increment in systolic blood pressure and up to eight-fold in the presence of diabetes.5,6 Physical inactivity and obesity independently increase the risk for IHD, in addition to predisposing individuals to other cardiovascular risk factors (e.g., hypertension, dyslipidemia, and diabetes). 

Wong BW, Wong D, McManus BM. Characterization of fractalkine (CX3CL1) and CX3CR1 in human coronary arteries with native atherosclerosis, diabetes mellitus, and transplant vascular disease. Cardiovasc Pathol 2002 ll(6) 332-338. 

As noted above, obesity is a health problem. It is associated with both elevated mortality and morbidity. More specifically, obesity is a risk factor for cardiovascular disease, including heart attack and stroke, and for high blood pressure (hypertension), diabetes, and hyperlipidemia (elevated levels of lipids in the blood, a risk factor for atherosclerosis and its sequelae), and for cancer. 

The three fat fuels and their metabolism are involved directly or indirectly in diseases such as diabetes mellitus, syndrome X, obesity, atherosclerosis and coronary heart disease, which are discussed in other chapters in this book. This section considers the problems associated with high blood levels of ketone bodies and long-chain fatty acids. 

Cantero, A. V., Portero-Otin, M., Ayala, V., Auge, N., Sanson, M., Elbaz, M., Thiers, J. C., Pamplona, R., Salvayre, R., and Negre-Salvayre, A. (2007). Methylglyoxal induces advanced glycation end product (ages) formation and dysfunction of PDGF receptor-beta Implications for diabetic atherosclerosis. FASEB J. 21,3096-3106. 

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