Flow affects development of intimal hyperplasia after arterial injury in rats.

Abstract

This study examined the effects of blood flow on intimal hyperplasia after balloon catheter injury of the rat common carotid artery. Flow was altered by ligation of the opposite common carotid artery (increased flow) or of the ipsilateral internal carotid artery (decreased flow). Blood flow decreased by 35% in the low-flow group and increased by 29% in the high-flow group. Similar changes in mean velocity were observed. Cross-sectional intimal area was significantly greater in the low-than the high-flow group at 2 weeks (0.11 ±0.01 versus 0.06±0.01 mm 1 ,p<0.01) and 4 weeks (0.17±0.02 versus 0.12±0.01 mm\/>=0.01) but not at 1 or 8 weeks. Smooth muscle cell proliferation rates (thymidine labeling indexes) were not different in high-and low-flow groups at 2 days and at 1 and 4 weeks. Matrix accumulation at 2 and 4 weeks was the same in both groups. Mature neointima did not respond to changes in flow; when vessel ligation was delayed until 2 months after injury, there was no effect on neointimal area. These data indicate that early neointimal hyperplasia is increased when flow is reduced, possibly because of alteration of smooth muscle cell migration. {Arteriosclerosis and Thrombosis 1992;12:963-971) KEYWORDS • tritiated thymidine • smooth muscle cells • animal models • rats • carotid artery • intimal hyperplasia C hanges in shear rate affect arterial structure in both normal and diseased vessels. During development, arterial caliber varies with shear rate, and in mature arteries, diameter increases when flow is augmented and decreases when flow is diminished. 1 -8 This regulation of vessel diameter results in maintenance of normal shear stress. Shear modulates structure in diseased vessels as well. Atherosclerotic plaques, intimal hyperplasia after angioplasty, and vein graft thickening are all increased in areas of low shear. 9 -18 The purpose of this study was to examine the effect of shear in a well-established model of intimal hyperplasia after balloon catheter injury of the rat common carotid artery. 19 -21 Flow through the injured artery was altered by ligation of the opposite common carotid artery (increased flow) or of the ipsilateral internal carotid artery (decreased flow). There was significantly more intimal hyperplasia in the decreasedflow group. Because the endothelium was absent in the injured vessel, this finding suggests that luminal smooth muscle cells (SMCs) respond to alterations in shear and can modify the function of underlying SMCs to modify vessel wall structure. Methods SurgeryMale Sprague-Dawley rats weighing 350-400 g (Tyler Laboratories, Seattle, Wash.) were anesthetized with intraperitoneal ketamine (225 mg/kg body wt) and xylazine (15 mg/kg body wt). Both common carotid arteries and the left internal carotid artery were exposed through a midline neck incision. A 2F balloon catheter was advanced through the left femoral artery into the left common carotid artery. The catheter was rotated as it was passed three times through the carotid artery, with the balloon distended sufficiently ...

Increased Flow and Shear Stress Enhance In Vivo Transforming Growth Factor-β1 After Experimental Arterial Injury

“…29 Hemodynamic forces have been shown to modulate intimal hyperplasia (IH) at regions prone to atherogenesis 30 and to restenosis after percutaneous transluminal coronary angioplasty 31 by regulation of VSMC proliferation 32 and migration. 6 Kohler and Jawien 6 showed that early IH is increased when flow is reduced after balloon injury of the rat carotid artery. Their study suggests that enhanced flow attenuated VSMC migration more than proliferation, suggesting that VSMC migration affected more than smooth muscle cell growth by flow.…”

“…[1][2][3] More specifically, reduced wall shear stress (WSS) has been shown to be associated with enhanced intimal lesion formation in atherosclerosis, 4 vascular grafts, 5 and balloon-injured vessels. 6 Conversely, relative elevations of blood flow and shear stress appear to have an atheroprotective role and inhibit intimal thickening after vascular injury. [7][8][9] Hemodynamic forces have been shown to modulate endothelial and vascular smooth muscle cell (VSMC) responses, which involve the induction of cytokines, such as platelet-derived growth factor (PDGF), basic fibroblast growth factor, and transforming growth factor-␤1 (TGF-␤1), 10,11 in addition to other mediators, such as nitric oxide, 7 tissue plasminogen activator, 12,13 and matrix metalloproteinases (MMPs), 1 4 involved in vascular remodeling.…”

Remodeling of Small Intramyocardial Coronary Arteries Distal to a Severe Epicardial Coronary Artery Stenosis

“…24 Changes in the fluid mechanical force from altered blood flow (shear stress) have direct effects on artery wall structure during growth and development 25 and on the progression of atherosclerosis and intimal hyperplasia. 26,27 An increase in shear stress or blood flow results in outward remodeling, which increases vessel size. In contrast, inward remodeling with reduced vessel size occurs in low-flow states with reduced shear stress.…”

Adenovirus-Mediated Human Tissue Kallikrein Gene Delivery Inhibits Neointima Formation Induced by Interruption of Blood Flow in Mice

“…[27][28][29] Therefore, we thought it would be worthwhile to evaluate the efficacy of HK gene delivery in preventing the vascular remodeling caused by permanent alteration in shear stress conditions. To this aim, we exploited the mouse model recently established by Kumar and Lindner, 20 in which disruption …”