Review Question - QID 106826

Endothelial dysfunction due to the development of fatty streaks marks the advent of atherosclerosis. Thus, nitric oxide (and prostacyclin) levels are decreased.

Normal microvascular endothelial cells are impermeable to large molecules, anti-inflammatory, and resistant to leukocyte adhesion and thrombosis. Perhaps most significantly, they promote vasodilation by upregulating nitric oxide and prostacyclin, which cause smooth muscle relaxation. Lipoprotein entry and modification and leukocyte recruitment causes local inflammation and endothelial injury impair production of nitric oxide and prostacyclin, allowing vasoconstriction (through direct smooth muscle contraction) from platelet products such as serotonin and thromboxane A2 to progress unchecked.

Lin summarizes the evidence and guidelines regarding the use of aspirin for ischemic heart disease / acute coronary syndrome prevention. He recognizes that the chronic burden of atherosclerosis is not limited in its manifestation to the heart, but also the peripheral vasculature. Mechanistically, aspirin decrease production of thromboxane A2, allowing what nitric oxide that can be released from endothelial cells to allow vasodilatation.

Li et al. discuss a mechanism by which atherosclerosis decreases nitric oxide production. Reactive oxygen species (ROS) normally are neutralized by antioxidant enzyme systems in the vasculature, but atherosclerosis increases ROS production, causing oxidation of those very enzymes. This renders endothelial nitric oxide synthases vulnerable to damage and thus decreased nitric oxide.

Incorrect Answers:
Answers 1-2: Serotonin and thromboxane A2 are released products of activated platelets, which are increased in atherosclerosis.
Answers 4-5: Atherosclerosis later involves leukocyte recruitment and the upregulation of proinflammatory cytokines like interleukin 1 and tumor necrosis factor.