Prof. Gerard Pasterkamp ,
Change in arterial size, arterial remodeling, is a major determinant of arterial occlusive disease. Moreover, the modes of arterial remodeling, expansion or constriction, are associated with atherosclerotic plaque characteristics. Expansive remodeling of the atherosclerotic plaque is a double edged sword: on one hand it prevents occlusion of the lumen by plaque growth, on the other hand the plaque seems more prone to rupture and thrombosis.
Atherosclerotic plaque formation has long been considered the only determinant of arterial occlusive disease. Although it was recognised that arteries can adapt their geometry in response to blood flow increase, it took more time to appreciate the effect of this geometrical remodeling response on atherosclerosis induced luminal narrowing. Just seventeen years ago it was described in human primates and human post mortem studies that radial enlargement of vessels can occur in response to progressive plaque growth [1,2]. The last decade, scientific interest in the role of arterial remodeling in occlusive arterial disease boomed with the use of the visualisation technique of intravascular ultrasound (IVUS) [3,4]. At first it was assumed that arteries were only capable of undergoing expansive remodeling in response to local plaque formation. This enlargement temporarily prevented lumen loss by compensating for plaque growth . However, the observation that arteries may also fail to enlarge or, even worse, may shrink when plaque accumulates turned the geometrical remodeling response into an important determinant of lumen loss [4-6]. With identical plaque formation, the local remodeling response will influence the lumen size varying from luminal enlargement when overcompensation takes place to total occlusion when constrictive remodeling is prevalent.
How strong is the effect of this segmental change in vessel size, e.g. remodeling, compared to local changes in plaque size on the diameter of the lumen? In previous studies we already demonstrated that only a weak relation exists between arterial plaque load and lumen area . In a more recent IVUS study in 609 patients we measured the lumen, plaque and vessel areas (= plaque + lumen area) at the site with most severe luminal obstruction and compared those with the lumen, plaque and vessel areas at a proximal and distal reference site . For each lesion we calculated the axial changes in lumen, plaque and vessel area (for example: axial change in lumen area = lumen area reference – lumen area lesion). In this large patient group the frequency distribution revealed a comparable width of the 95% confidence intervals for segmental variation in plaque area and vessel area [–1.02 mm2, +11.56 mm2] and [–6.44 mm2, +5.04 mm2], respectively. Thus, surprisingly, in a large population suffering from coronary atherosclerotic disease, average segmental axial variation in vessel area equaled that of plaque area (see confidence intervals).This observation supports the concept that arterial remodeling is a major determinant of luminal narrowing in de novo atherosclerosis.
A similar study was also performed in 125 atherosclerotic femoral arteries in which the lumen, plaque and vessel areas were measured in a total of 3266 segments. In these femoral arteries we observed that when, on average, lumen area decreased (from 21.8 mm2 to 7.0 mm2), the average increase in plaque area could only explain a minor part of the decrease in lumen (plaque increased from 10.3 to 16.5 mm2). On the other hand, segmental decrease in vessel area appeared to be the main determinant of lumen decrease (32.1 to 23.5 mm2) .
In summary, the role of arterial geometric remodeling in de novo atherosclerotic occlusive disease is undervalued and why so little research is aimed at developing intervention strategies to influence the remodeling mode is an enduring question, but the answer is not that difficult: knowledge on biological and mechanical triggers that induce these segmental remodeling responses is lacking. To gain more insight in the mechanisms of expansive remodeling, animal models reflecting human like atherosclerotic disease are needed. In contrast to expansive remodeling, constrictive remodeling has not been described in atherosclerotic animal models. Insight in the processes that trigger and direct the different remodeling modes (expansion or constriction) may help us in developing new therapeutic strategies to overcome or prevent luminal narrowing.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
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Pasterkamp G, Wensing PJW, Post MJ, Hillen B, Mali WPTM, Borst C. Paradoxical arterial wall shrinkage contributes to luminal narrowing of human atherosclerotic femoral arteries. Circulation 1995;91:1444-1449. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7867185&dopt=Abstract
Pasterkamp G, Borst C, Post MJ, Mali WPTM, Wensing PJW, Gussenhoven EJ, Hillen B. Atherosclerotic arterial remodeling in the superficial femoral artery: individual variation in local compensatory enlargement response. Circulation 1996;93:1818-1825 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8635261&dopt=Abstract
Nishioka T, Luo H, Eigler NL, Berglund H, Kim CJ, Siegel RJ. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study. J Am Coll Cardiol 1996;27:1571-1576. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8636538&dopt=Abstract
Pasterkamp G, Fitzgerald P, de Kleijn DPV. Expansive arterial remodeling: a sheep in wolf’s clothes. J Vasc Research, 2002;39(6):514-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12566977&dopt=Abstract
Vink A, Schoneveld AH, Borst C, Pasterkamp G. The contribution of plaque and constrictive remodeling to de novo atherosclerotic luminal narrowing in the femoral artery. J Vasc Surgery, 2002 36(6):1194-8 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12469038&dopt=Abstract
Dr. G. Pasterkamp Utrecht, Netherlands Nucleus member of the Working Group on Pathogenesis of Atherosclerosis
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