At the level of the endothelium, nitric oxide (NO) causes the following except:
Increased smooth muscle proliferation. NO has important effects on the endothelium to produce vasodilation, reduced leukocyte adhesion and platelet reactivity, and downregulation of oxidative enzymes. Consistent with these beneficial effects, NO results in a reduction in smooth muscle proliferation, not an increase.
The following cells are considered most important to the process of atherosclerosis:
Monocyte/macrophage lineage. These cells bind oxidized LDL to form foam cells, which then release proinflammatory cytokines to perpetuate the atherosclerotic process.
The following are characteristics of a vulnerable plaque except:
High concentration of collagen. It is in fact the low concentration of collagen (due to low levels of smooth muscle cells) that results in the collagen-poor thin cap of vulnerable plaques. These plaques display high concentrations of macrophages (foam cells) and T-lymphocytes (producing interferon-γ), as well as significant neovascularization and a large necrotic core that is vulnerable to rupture and propagate thrombosis. In fact, saphenous vein graft (SVG) lesions tend to have a larger necrotic core than native coronary lesions, which is one factor that contributes to greater plaque friability and worse outcomes with SVG stenting.
Arterial thrombosis after plaque rupture is initiated by:
Tissue factor. Tissue factor binding to factor VII is the initiating event for the extrinsic blood coagulation cascade. The complex can also cleave factor IX and contribute to activation of the intrinsic cascade as well. Tissue factor is normally not expressed in the vasculature, but, in atherosclerotic vessels, tissue factor is expressed by macrophages and smooth muscle cells. Tissue factor expression is increased in the lesions of patients who present with unstable angina. On plaque rupture, the exposure of tissue factor to bloodborne coagulation factors leads to thrombus formation.
Low levels of gene expression can be detected by:
Reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR is capable of finding a single copy of RNA. Northern blot analysis requires at least 5 to 10 μg of total RNA. Western blot analysis is for determining protein levels. Southern blot analysis is for genotyping and requires multiple copies of DNA. Gene transfer is not a detection method.
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