Peripheral Vascular Stenosis in Apolipoprotein E-Deficient Mice

Abstract

A systematic analysis of the distribution of advanced atherosclerotic lesions was undertaken in chow-fed, 9-month-old apolipoprotein (apo) E-deficient mice to identify sites amenable for study of mechanisms of formation of stenotic lesions. The arterial tree was dissected intact and included medium-sized arteries in the extremities as well as arteries of the head and neck. The most reproducible lesions were seen in the ascending aorta and in the carotid, femoral, and popliteal arteries. Casting of the vascular tree provided additional verification of the presence of lumen narrowing in the external branches of the carotid artery. Consistent with what has been observed in human atherosclerotic arteries, there was dilation in response to lesion growth and no correlation between lesion mass and lumen loss in the mouse arteries. This adaptation was especially true in the ascending aorta, where normal lumen size was maintained at atherosclerotic sites. In contrast, the external carotid arteries were stenotic in 9 of 12 animals. Here too, however, loss of lumen did not correlate with lesion mass but did correlate with adventitial inflammation and medial atrophy. Lumen narrowing also occurred most frequently at sites where extracellular cholesterol clefts were a prominent part of the lesion. These data suggest that the stenotic process in advanced atherosclerotic vessels may depend on death of medial smooth muscle cells, possibly in response to inflammatory changes in the plaque or adventitia.

Effect of Immune Deficiency on Lipoproteins and Atherosclerosis in Male Apolipoprotein E–Deficient Mice

“…31 A similar arterial remodeling was noted in the peripheral arteries of apoE°male mice. 32 At the time of euthanasia, compared with the apoE°mice, the apoE°RAG2°mice were lower in body weight. We have no obvious explanation for this observation.…”

Regulation of the Platelet-derived Growth Factor Receptor-β by G Protein-coupled Receptor Kinase-5 in Vascular Smooth Muscle Cells Involves the Phosphatase Shp2

“…Nine-month-old mice were sacrificed, and the circulatory system was perfused with lactated Ringer solution at 80 mm Hg pressure. The common carotid arteries were excised, embedded in OCT compound, frozen at Ϫ150°C, and sliced at 5 m on a cryotome to obtain sections of the distal common carotid, just proximal to the carotid bifurcation (a site commonly involved with atherosclerosis in the 9-month-old apoe Ϫ/Ϫ mouse) (22). Sections were fixed and permeabilized with methanol/acetone (50:50) at room temperature for 2 min, washed twice in Dulbecco's PBS for 1 min, and then incubated (25°C) for 30 min in "blocking buffer": 3% (w/v) bovine serum albumin in TTBS (0.02% (v/v) Tween 20, 10 mM Tris-Cl, pH 7.4, 140 mM NaCl).…”

Apolipoprotein E Inhibits Platelet-derived Growth Factor-induced Vascular Smooth Muscle Cell Migration and Proliferation by Suppressing Signal Transduction and Preventing Cell Entry to G1 Phase

“…Fifth, apoE inhibits agonist-induced platelet aggregation (43), which will retard the progression of atherosclerotic lesion; and sixth, apoE suppresses growth factor and oxLDL-induced smooth muscle cell migration and proliferation (this study). Taken together, these apoE activities may explain the versatility of this apolipoprotein in conferring protection against various forms of vascular diseases, including cholesterol-induced atherosclerosis (2), angioplasty-or injuryinduced restenosis (10,12,44), and transplant-induced accelerated arteriosclerosis (46).…”