doi: 10.1161/01.CIR.0000157072.64410.01
(Circulation. 2005;111:e119.)
© 2005 American Heart Association, Inc.
Correspondence |
Letter Regarding Article by Korshunov and Berk, "Strain-Dependent Vascular Remodeling: The ‘Glagov Phenomenon’ Is Genetically Determined"
Department of Cardiology, Biomedical Engineering, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Drs Korshunov and Berk1 described the modulation of vascular remodeling in response to a sudden decrease of shear stress induced by partial ligation of the carotid artery of different mouse strains. Although a similar study was previously conducted with similar mouse strains in which the carotid artery was totally occluded,2 Korshunov and Berk argued that their partial ligation model is more relevant to human carotid intima-media thickness and coronary atherosclerosis and concluded from their measurements that the Glagov phenomenon has a genetic background.
To strengthen the relevance of their data, the authors compared their results—outward remodeling under low flow conditions—to our data in human atherosclerotic coronary arteries.3 Indeed, we found that in segments with lumen preservation because of outward vascular remodeling, atherosclerotic plaques were observed at relatively low shear stress regions.3 Because vascular remodeling is defined as an average over the cross section and the shear stress varies over a cross section in (curved) coronary arteries, however, it is not possible to evaluate the relationship between local vascular remodeling and eccentric low shear stress. Although attempts have been made to relate local eccentric vascular remodeling to shear stress,4 no unambiguous method to do so exists. In contrast to Korshunov and Berk, we interpreted our data as follows.3 In the presence of atherosclerotic risk factors, plaques start to develop eccentrically at low shear stress regions. Over time, when plaques grow and encroach into the lumen, the shear stress increases over the whole cross section, including the nondiseased plaque-free wall. Because vascular remodeling is a natural response of healthy arteries to control shear stress, the increased shear stress at the plaque-free wall induces outward remodeling, preventing lumen narrowing. Glagov already addressed the likely role of the plaque-free vessel wall in outward vascular remodeling.5 Thus, the outward remodeling in human arteries during plaque development, which prevents lumen narrowing (the Glagov phenomenon5), was explained as a response to increased shear stress. Therefore, the relevance of studying the Glagov phenomenon as a response to sustained decreased shear stress in nonatherosclerotic mice is not in line with our observations or those of Glagov.
To further relate their data to Glagov’s observations,5 Korshunov and Berk plotted lumen area relative to stenosis to determine a cutoff value for vascular remodeling, as observed in human atherosclerotic plaques. Translating the data from their Figure 5 into their Figure 6 lead to the conclusion that only one mouse strain (SJL) was responsible for the data that showed >55% stenosis. Therefore, generalization of this cutoff value for vascular remodeling seems inappropriate.
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 Top References References |
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1. Korshunov VA, Berk BC. Strain-dependent vascular remodeling: the "Glagov phenomenon" is genetically determined. Circulation. 2004; 110: 220–226.
2. Harmon KJ, Couper LL, Lindner V. Strain-dependent vascular remodeling phenotypes in inbred mice. Am J Pathol. 2000; 156: 1741–1748.
3. Wentzel JJ, Janssen E, Vos J, Schuurbiers JC, Krams R, Serruys PW, de Feyter PJ, Slager CJ. Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling. Circulation. 2003; 108: 17–23.
4. Stone PH, Coskun AU, Kinlay S, Clark ME, Sonka M, Wahle A, Ilegbusi OJ, Yeghiazarians Y, Popma JJ, Orav J, Kuntz RE, Feldman CL. Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans: in vivo 6-month follow-up study. Circulation. 2003; 108: 438–444.
5. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987; 316: 1371–1375.[Abstract]
Response
Center for Cardiovascular Research, Department of Medicine, University of Rochester, Rochester, NY, bradford_berk{at}urmc.rochester.edu
In their letter, Wentzel et al ask: Can the Glagov phenomenon be studied in nonatherosclerotic mice by inducing low shear stress conditions? The first issue is how to evaluate the relationship between local vascular remodeling and local shear stress. Recent human studies1 have shown that sites of high shear stress (
>38 dyne/cm2) remodel by decreasing plaque area and increasing lumen without changes in vessel size. At sites with low shear stress ( <9 dyne/cm2), lumen was maintained, despite an increase in plaque size, via an increase in vessel size. At intermediate values of shear stress (9<<38 dyne/cm2), both processes occurred. These data suggest that vascular remodeling as described by Glagov can occur in regions with both low and high shear stress, although different mechanisms appear to be responsible.
A second issue is whether local remodeling is driven by the "plaque-free" artery. No data exist to support the assertion that plaque-free portions of the artery mediate remodeling. Wentzel et al2 published data consistent with our findings that regions of low shear stress are highly associated with intima-media thickening (IMT) and outward remodeling in humans. The key finding of our article3 was that IMT is the driving force for outward remodeling.
Wentzel et al noted that only one mouse strain (SJL) was responsible for the failure to remodel when IMT occupied >55% of lumen area. In fact, the contribution for the strains was as follows: SJL 74%, FVB 20%, C57 5%, and DBA 1%. These results suggest multiple genetic contributions in several strains.
Finally, Wentzel et al state that it is not realistic to study the Glagov phenomenon in nonatherosclerotic mice. We respectfully disagree and suggest that the initial events in vascular remodeling that are associated with atherosclerosis involve IMT. Thus, the present study is relevant to the mechanisms by which vascular remodeling is initiated, even in atherosclerosis.
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References |
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TopReferencesReferences |
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1. Stone PH, Coskun AU, Kinlay S, Clark ME, Sonka M, Wahle A, Ilegbusi OJ, Yeghiazarians Y, Popma JJ, Orav J, Kuntz RE, Feldman CL. Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans: in vivo 6-month follow-up study. Circulation. 2003; 108: 438–444.
2. Wentzel JJ, Janssen E, Vos J, Schuurbiers JC, Krams R, Serruys PW, de Feyter PJ, Slager CJ. Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling. Circulation. 2003; 108: 17–23.
3. Korshunov VA, Berk BC. Strain-dependent vascular remodeling: the "Glagov phenomenon" is genetically determined. Circulation. 2004; 110: 220–226.
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