Structure of carotid artery in baboon and rat and differences in their response to endothelial denudation angioplasty

Toit, D. Du; Aavik, Einari; Taskinen, Eero; Myburgh, Ettienne J.; Aaltola, Eva M.; Aimonen, Merja; Aavik, Silja; Wyk, Joban van; Häyry, P

doi:10.3109/07853890109002061

Cited by 15 publications

(17 citation statements)

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“…The "cell-rich" character of baboon carotid neointima turns more fibrillar from day 14 postinjury onwards (4). This coincided with the progressive and often sustained expression of several connective tissue genes.…”

Section: Discussionmentioning

confidence: 95%

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Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury

Aavik

Mahapatra²,

Boldrick³

et al. 2004

FASEB j.

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Treatment for fibroproliferative restenosis after angioplasty and endovascular surgery is an unmet medical need. Rational therapy and drug design still lack the very basic knowledge about the underlying biological processes leading to pathological changes in the vessel wall. We have developed a primate model for vascular response to denudation-overstretch injury of baboon carotid artery. With this model, we have investigated the time course of vascular expression of 41,000 human cDNA clones and correlated these changes with carotid histology and function. Analysis revealed 20,788 differentially regulated cDNA clones. After high stringency data selection, the most prominently regulated 1629 cDNA clones representing 1510 genes of known function were clustered. Genes corresponding to functional and anatomical alterations in the injured carotid wall were further aligned into functional groups according to Gene Ontology classification. The observed expression patterns faithfully reflected the functional and anatomical alterations observed in the vascular wall in response to injury. The analysis presents a tentative model for genomic response to balloon catheter injury and a road map to identify time-related genomic alterations in human vascular specimens.

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Section: Discussionmentioning

confidence: 95%

“…Having these differences in mind, we developed a baboon model for carotid overstretch endothelial denudation injury (4).…”

mentioning

confidence: 99%

Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury

Aavik

Mahapatra²,

Boldrick³

et al. 2004

FASEB j.

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“…Although both replication and migration seem to contribute to the intimal injury response, it has been proposed that the role of migration is more important than that of replication [24]. In this study, the peak in explant proliferation ([ 3 H]TdR incorporation) was observed on day 7 after injury, most likely reflecting the peak in in vivo neointimal proliferation at that time [12].…”

Section: Discussionmentioning

confidence: 73%

Vascular Cell Kinetics in Response to Intimal Injury ex vivo

Tigerstedt

Savolainen-Peltonen²,

Lehti³

et al. 2009

J Vasc Res

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Background: Recent studies indicate that the smooth muscle-like cells contributing to neointimal hyperplasia after vascular injury derive from circulating precursor cells. Here, we define the time course of precursor cell influx, the roles of separate vascular layers, and the relative role of migration versus proliferation to intimal hyperplasia. Methods and Results: After rat aortic denudation injury the neointimal cell number increased several 100-fold between days 4 and 28, preceded by a 5-fold increase in the number of adventitial cells and a 4-fold increase in the number of adventitial microvessels. The influx, migration, and maturation of neointimal cells were quantitated by culturing whole vessel explants at different time points after injury. Explant outgrowth increased 14-fold, and cell migration 3.5-fold on days 2–14 after injury. Cell proliferation increased less than 2-fold. The frequency of precursors to outgrowing cells, determined using limiting dilution analysis, increased 8-fold between days 2 and 4 after injury. Many outgrowing cells displayed characteristics of undifferentiated cells. Conclusions: Adventitial activation precedes development of the neointima, and precursor cell influx occurs on days 2–14 after injury. Cell migration, more than proliferation, contributes to fibrointimal dysplasia. These findings underline the importance of early therapeutic intervention with antimigratory compounds to prevent neointimal hyperplasia.

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“…Human arteries, as well as the arteries of subhuman primates, have an intima that develops with age (44). Studies in South Africa indicated that if you feed baboons with hospital cafeteria food for more than three years, they die of stroke.…”

Section: Chronic Rejection and Long-term Resultsmentioning

confidence: 98%

Medawar Prize Acceptance Speech

Häyry

2006

Transplantation

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Structure of carotid artery in baboon and rat and differences in their response to endothelial denudation angioplasty

Abstract: Baboon carotids are very different from rat carotids both in their native structure and in their response to injury. With the limited amount of information available from human vessels, baboon carotids closely resemble human carotids in both respects.

Cited by 15 publications

References 50 publications

Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury

Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury

Vascular Cell Kinetics in Response to Intimal Injury ex vivo

Medawar Prize Acceptance Speech

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