Remodeling With Neointima Formation in the Mouse Carotid Artery After Cessation of Blood Flow

Abstract

The ability of gene targeting in the mouse species presents a powerful tool to determine the role of specific molecules in vascular biology. Using a denuding-injury procedure, we recently reported that intimal lesions can be induced in the carotid artery of outbred mice. The technical challenge associated with achieving complete denudation and the relatively small size of the developing lesions prompted us to design the present model of neointima formation and vascular remodeling in the carotid artery of the inbred FVB mouse strain. Complete ligation of the vessel near the carotid bifurcation induced rapid proliferation of medial smooth muscle cells, leading to extensive neointima formation in the presence of an endothelial lining. Thrombus formation was not observed except in the most distal part of the vessel adjacent to the ligature. At 4 weeks after ligation, luminal area was reduced by approximately 80% through a combination of decreased vessel diameter and neointima formation. Ultrastructural analysis provided evidence for cell death in the developing neointima as well as the remodeling media. The present model might be useful in identifying those genes important for neointima formation and vascular remodeling.

High Glucose Inhibits Apoptosis Induced by Serum Deprivation in Vascular Smooth Muscle Cells via Upregulation of Bcl-2 and Bcl-xl

“…Recent studies (20,21) have suggested that vascular re- modeling and lesion formation are determined in part by the balance between cell proliferation and apoptotic cell death. Cho et al (22) reported that reduction in blood flow in animal models resulted in reduction in VSMC number by apoptosis (22,23). Acute arterial injury is followed by rapid induction of medial cell apoptosis from 30 min to 4 h (24,25).…”

Myristoylated Alanine‐Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation

“…Mice were anesthetized and a 1‐cm midline anterior cervical incision was made. To induce intimal hyperplasia, the carotid artery was ligated at the bifurcation as described in the literature 34. Animals were allowed to recover and were subsequently euthanized at predetermined time points.…”

Andrographolide inhibits NF-κB activation and attenuates neointimal hyperplasia in arterial restenosis

“…Through a midline incision in the neck, the left common carotid artery was looped proximally to the carotid bifurcation and ligated completely by a 7-0 propylene suture to disrupt blood flow [14,15]. In the groups receiving treatment, Andro, 4H-Andro (5 μg/g of body weight) or DMSO (in equal volume to the Andro group) was administered every second day beginning on day 0.…”

“…The de novo synthesis of E-selectin and VCAM-1 in vascular endothelial cells is well known to be exclusively regulated by NF-κB transcription factors [9,[14][15][16][17][18][19][20]. We thus examined whether the expression of E-selectin and VCAM-1 is regulated by p50-mediated NF-κB activation in our murine models of experimental arterial restenosis.…”