Time course of vascular remodeling, formation of neointima and formation of neoadventitia after angioplasty in a porcine model

Mæng, Michael; Olesen, Peter Grønning; Emmertsen, Niels C.; Thorwest, Martin; Nielsen, Torsten Toftegaard; Kristensen, Bent Bruun; Falk, Erling; Andersen, Henning

doi:10.1097/00019501-200106000-00004

Cited by 27 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we found a significant increase in the number of vasa vasorum in the adventitia of the carotid arteries, and a corresponding trend in the RCx and renal arteries, as assessed by immunohistochemistry of factor-VIII-related antigen. This supports the concept of induced angiogenesis in the adventitia in response to vessel injury, as previously shown in the coronary-artery system with and without atherosclerotic plaques [46,47,48,49]. Recently published data reported the existence of endothelial precursor and stem cells in the area between the smooth-muscle cells and the adventitial layer in the human adult vascular wall.…”

Section: Discussionsupporting

confidence: 88%

Resistance of the Internal Mammary Artery to Restenosis: A Histomorphologic Study of Various Porcine Arteries

Horstick

Bierbach²,

Schlindwein³

et al. 2007

J Vasc Res

View full text Add to dashboard Cite

Background/Aims: Restenosis after percutaneous transluminal angioplasty (PTA) of the internal mammary artery (IMA) grafts is much less pronounced than in other arteries and venous grafts. The aim of the study was to test whether various arteries respond differently to dilatation. Methods: PTA of the IMA, carotid, renal and circumflex coronary (RCx) arteries was performed in 9 pigs (balloon to artery ratio of 1:1.5). After 8 weeks, angiography was repeated and vessels prepared for histological analysis. Immunohistochemical staining was done to examine proliferative activity (Ki67) and to identify the vasa vasorum of the adventitia (F VIII-RA). Results: The intima-media ratio after PTA was lowest in the IMA (0.06), followed by the carotid (0.27) and renal arteries (0.49) and the RCx (0.69). Proliferation of the intima was seen at 287° of the vessel circumference in the RCx, at 286° in the renal and at 166° in the carotid artery. No proliferative activity was seen in the IMA. The intima-adventitia ratio was lower in the IMA than in the RCx and renal arteries (p < 0.05). Conclusion: Intima proliferation after PTA varies between the different vessels, with best results seen in the IMA. There are differences in remodeling after PTA between muscular, muscular/elastic and elastic arteries.

show abstract

Section: Discussionsupporting

confidence: 88%

Resistance of the Internal Mammary Artery to Restenosis: A Histomorphologic Study of Various Porcine Arteries

Horstick

Bierbach²,

Schlindwein³

et al. 2007

J Vasc Res

View full text Add to dashboard Cite

show abstract

“…Sensing the intimal and medial injury, the tunica adventitia responds with robust cell proliferation, matrix remodeling and elaboration of inflammatory cells and cytokines. 2, 3 In addition to fibroblasts/myofibroblasts and residential immune cells, stem cells or progenitor cells are now believed to reside within the adventitia. 4–6 Evidence supporting the potential migration of adventitial cells through the media and into the neointima is derived mostly from animal studies involving selective labeling of adventitial cells or transplanting cultured adventitial cells onto the adventitial side and monitoring movement of these cells following arterial injury.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase C-Delta Mediates Adventitial Cell Migration Through Regulation of Monocyte Chemoattractant Protein-1 Expression in a Rat Angioplasty Model

Ren

Wang

et al. 2012

ATVB

View full text Add to dashboard Cite

Objective The adventitia is increasingly recognized as an important player during the development of intimal hyperplasia. However, the mechanism of adventitial cell recruitment to the subintimal space remains largely undefined. We have shown previously that gene transfer of protein kinase C-delta (PKCδ) increases apoptosis of smooth muscle cells (SMCs) following balloon injury. In the current study, we investigated a potential role of PKCδ in regulating the recruitment of adventitial cells. Methods and results Conditioned media from PKCδ-overexpressing SMCs stimulated migration and CCR2 expression of adventitial fibroblasts through a MCP-1 dependent mechanism. Following balloon injury of rat carotid arteries, overexpression of PKCδ in SMCs significantly increased MCP-1 and CCR2 expression and the number of adventitia-originated cells detected in the neointima. Administration of an anti-MCP-1 antibody markedly diminished the recruitment of adventitial cells. Combined PKCδ overexpression and anti-MCP-1 inhibited initmal hyperplasia more effectively than either approach alone. Conclusions Our data suggest that PKCδ regulates recruitment of adventitial cells to the neointima via a mechanism involving upregulation of the MCP-1/CCR2 signaling axis in injured arteries. Blockage of MCP-1 while enhancing apoptosis may serve as a potential therapeutic strategy to attenuate intimal hyperplasia.

show abstract

“…Coronary angioplasty is an established procedure in domestic swine with normal cholesterol levels. The key problem with this model is that the arteriosclerotic pathology differs from that in human; the lesions have abundant fibrotic tissue with little necrotic core formation [ 26 ]. Our investigation of temporal changes in histological tissues from our model pigs revealed human-like atherosclerotic lesions containing a lipid pool at four and eight weeks, and predominant fibrous components at 12 weeks.…”

Section: Discussionmentioning

confidence: 99%

Development of Accelerated Coronary Atherosclerosis Model Using Low Density Lipoprotein Receptor Knock-Out Swine with Balloon Injury

et al. 2016

View full text Add to dashboard Cite

BackgroundSeveral animal models have facilitated the evaluation and pathological understanding of atherosclerosis, but a definitive animal model of coronary atherosclerosis is not available. We therefore developed low density lipoprotein receptor knockout (LDLR-KO) pigs with hypercholesterolemia, a model which rapidly developed coronary atherosclerosis following balloon injury.Methods and ResultsWe deleted LDLR exon regions from cultured porcine fetal fibroblasts and cloned LDLR knockout (LDLR-KO) embryos microinjecting fetal fibroblast nuclei into enucleated oocytes. Twelve LDLR-KO pigs were fed a 2.0% cholesterol and 20% fat diet. Baseline serum LDL cholesterol level was 510.0±86.1 mg/dL. Balloon injury was created in 46 coronary segments and necropsy were obtained 2, 4, 8 and 12 weeks later. Coronary artery sections were reviewed to evaluate lesion progression. We found lipid accumulation with foam cells and inflammatory cells beginning four weeks after balloon injury. The mean ratio of macrophages to plaque area was significantly higher in the four- weeks and eight-week animals compared with those at 2-weeks (8.79% ± 5.98% and 17.00% ± 10.38% vs. 1.14% ± 1.88%, P < 0.0001). At 12 weeks the ratio decreased toward the level at 2 week level (4.00% ± 4.56%, P = 0.66 vs. baseline). Advanced coronary atherosclerotic lesions contained lipid pools at eight-weeks with fibrous components beginning at 12 weeks.ConclusionsWe developed a model of rapid coronary atherosclerosis using LDLR KO pigs with balloon injury. This model may be useful for preclinical evaluation of medication or devices, and may also help investigate mechanisms of plaque progression.

show abstract

Time course of vascular remodeling, formation of neointima and formation of neoadventitia after angioplasty in a porcine model

Abstract: Formation of neoadventitia precedes late loss of lumen, constrictive remodeling, and formation of neointima. The time course of vascular remodeling coincides with growth of neointima rather than with changes in the adventitia.

Cited by 27 publications

References 25 publications

Resistance of the Internal Mammary Artery to Restenosis: A Histomorphologic Study of Various Porcine Arteries

Resistance of the Internal Mammary Artery to Restenosis: A Histomorphologic Study of Various Porcine Arteries

Protein Kinase C-Delta Mediates Adventitial Cell Migration Through Regulation of Monocyte Chemoattractant Protein-1 Expression in a Rat Angioplasty Model

Development of Accelerated Coronary Atherosclerosis Model Using Low Density Lipoprotein Receptor Knock-Out Swine with Balloon Injury

Contact Info

Product

Resources

About