Molecular analysis of arterial stenosis in rat carotids

Abstract

A new model of surgical injury for the induction and development of stenosis in common rat carotids is described. This model differs from balloon angioplasty or vein graft systems currently applied on animals to develop stenosis, since it involves the entire vessel wall layers and mimics the injury occurring during arterial grafts, endarterectomy or organ transplantation. At different times following arterial damage, the pattern of expression of genes already known to be involved in the proliferation, differentiation, and apoptosis of smooth muscle cells (c-myc, Angiotensin II receptor 1, Bcl-2 and Bax alpha), as well as of Rb and Rb2 genes, whose pattern of expression after arterial injury has not yet been reported, was analyzed by semi-quantitative reverse transcription-polymerase chain reaction technique. Histological and histochemical analysis on carotid sections shows the morphological changes which occurred 30 days after surgical injury in the vessel wall. Molecular and histological data demonstrate that this model of surgical injury induces neointimal proliferation in about 30% of rats. In about 70% of the remaining rats, it induces the processes responsible for negative remodelling, namely the significant accumulation of extracellular matrix and fibers and disorganization of arterial tunics. This model is therefore available for further studies on the expression of genes involved in the arterial stenotic process, as well as for testing drugs aimed at limiting this recurrent pathophysiological phenomenon.

Stenosis progression after surgical injury in Milan hypertensive rat carotid arteries

“…The surgical injury model we applied on MHS rat common carotid was performed as already published [21]. Briefly, a plastic Scanlon clamp for coronary artery bypass grafting was placed for 10 s on the carotid artery in order to cause a crushing lesion to the vessel.…”

“…The c-myc expression profile induced by vascular trauma in MHS (Fig. 1a) is similar to the pattern we previously detected in SHR carotids submitted to the same kind of injury [25], both showing higher activation rate in comparison to normotensive WKY rats [21].…”

Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells

“…Arteriotomy of rat common carotid artery was performed as already published [7]. Briefly, a plastic Scanlom clamp for coronary artery grafting was placed for 10 s on the carotid causing a crushing lesion to the vessel.…”

“…Data are presented as the mean±SEM. *:p<0.05 vs. DMEM-treated carotids induced in the chronic phase a marked neoadventitia along with extracellular matrix and elastic lamina accumulation in both groups of rats, with only limited focal neointima in a few cases [7,8]. In addition, internal and external elastic lamina and media disruptions at the injury site were evident, often with media substitution by fibrotic tissue.…”

“…We set up and validated an arteriotomy model of surgical injury of rat common carotid [7] alternative to the model of balloon angioplasty and that mimics the injury affecting the arteries submitted to grafting or endarterectomy, since it is characterized by an interruption of both the internal and external elastic laminae, considered clinically relevant for the development of arterial stenosis. In a previous study we highlighted the positive antirestenotic role played by allogenic MSCs in the arteriotomy model of rat vascular injury [8], homing at the injury site up to 7 days after arteriotomy and limiting the lumen stenosis 30 days later.…”