Roles of cardiovascular risk factors in endothelial nitric oxide synthase regulation: an update.

Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardiovascular risk factors on the vascular system. The current review provides the most updated research advances in the area of the regulation of the endothelial nitric oxide synthase-nitric oxide (eNOS-NO) system by several cardiovascular risk factors. There are many exciting discoveries made from the studies of several major cardiovascular risk factors such as hypertension, cigarette smoking, dyslipidemia and diabetes mellitus as well as emerging risk factors such as HIV infection, antiretroviral therapy, genomic variability, and cytokines. In general, cardiovascular risk factors could impair the eNOS-NO system with a variety of molecular mechanisms including decrease in NO bioavailability by excess reactive oxygen species, inhibition of eNOS expression and activity, and deficiency of eNOS cofactors. Special attention is paid to the impact of several new or emerging risk factors on cardiovascular disease and the eNOS-NO system. These mechanistic studies are clinically significant because they may lead towards new and effective strategies for the prevention and treatment of cardiovascular disease.