1.c. 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.
2.b. Monocyte/macrophage lineage. These cells bind oxidized LDL to form foam cells, which then release proinflammatory cytokines to perpetuate the atherosclerotic process.
3.b. 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.
4.e. 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 blood-borne coagulation factors leads to thrombus formation.
5.c. 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.
6.e. Glycoprotein (GP) IIb/IIIa receptor. ADP, collagen, and thrombin bind independently, leading to platelet activation and, ultimately, to expression of the GP IIb/IIIa receptor. GP IIb/IIIa receptor expression leads to platelet clumping by binding to surrounding activated platelets. The αvβ3 receptor does not lead to platelet aggregation.
7.c. Transforming growth factor-β (TGF-β). Platelet-derived growth factor-β, bFGF, and thrombin are all smooth muscle mitogens. Oxidized LDL causes smooth muscle cell proliferation through the autocrine release of bFGF. TGF-β alters the smooth muscle cell phenotype from a proliferative to a synthetic state and, thus, is antiproliferative.
8.a. Insulin-like growth factor-1β. Insulin-like growth factor-1β overexpression has been shown to be cardioprotective because of decreased apoptosis in the setting of myocardial ischemia. Dobutamine has been shown to induce cardiomyocyte apoptosis. Caspase 3 and Bid cleavage are cytoplasmic markers of apoptosis, but do not directly influence apoptosis itself.
9.d. Acetylcholine (ACh). ACh, acting through muscarinic receptors, exerts its effect on the endothelium by promoting the conversion of L-arginine to NO. This in turn produces smooth muscle cell relaxation and consequent vasodilation. ACh is therefore an endothelium-dependent vasodilator. In patients with endothelial dysfunction, this effect is lost, and the direct action of ACh on smooth muscle cells producing vasoconstriction is more pronounced. The other agents listed are all endothelium-independent vasodilators.
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