CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Yiannis Chatzizisis, MD, MSc,
Ahmet Umit Coskun, PhD,
Michael Jonas, MD,
Elazer R. Edelman, MD, PhD, FACC,
Charles L. Feldman, ScD and
Peter H. Stone, MD, FACC*
* Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115 (Email: pstone{at}partners.org).
Dr. Kaneda appropriately draws attention to the complexity of vascular remodeling. The magnitude of low endothelial shear stress (ESS), as well as changes in ESS and the rate of change in ESS, all contribute to the pathobiology of atherosclerosis (1,2). In our human pilot study, we observed expansive remodeling in areas of initially low or high ESS. It is therefore likely that expansive remodeling occurs through different mechanisms in different local environments and under different flow regimes (3).
Low ESS enhances lipid accumulation and local inflammation. The enzymatic degradation of the underlying internal elastic lamina and media that follow ultimately lead to expansive remodeling (1). Whether the expansive remodeling response becomes excessive or compensatory is likely dependent on the magnitude of low ESS (1). Very low ESS induces an intense inflammatory response that leads to excessive lumen and wall expansion (excessive expansive remodeling) (1). These wall changes further reduce local ESS, establishing a cascade of inflammation and excessive expansive remodeling, which can transform a stable plaque into a thin cap fibroatheroma. In contrast, in areas with limited reductions in ESS, local inflammation is modest, and the cellular reaction might strengthen the plaque and lead to compensatory expansive remodeling (1). The changes in the vessel wall and the minimal narrowing of the lumen might restore ESS to more physiologic levels and thereby promote plaque quiescence.
High ESS might also lead to expansive remodeling, but through a different mechanism. Reactive dilation of the plaque-free wall with normal flow-responsive endothelium in the area of an eccentric plaque can normalize the local ESS environment (4).
In our human pilot study (3), we observed that areas with low baseline ESS can develop constrictive remodeling at follow-up. Although the pathobiologic mechanisms responsible for constrictive remodeling are less clear than those of expansive remodeling, constrictive remodeling in our patients may have been related to subclinical plaque microrupture and subsequent healing (5). Alternatively, a fibroproliferative smooth-muscle cell phenotype may have been consistently operative throughout the natural history course of that plaque.
We agree that it is critical to understand these vascular behavior patterns in more detail because the ultimate clinical manifestations of coronary disease depend on the morphologic evolution and flow remodeling of the atherosclerotic plaque (1). Although clinical studies are essential to the identification of atherosclerotic patterns, animal models enable specific delineation of the dynamic and complex interactions among local flow, atherosclerosis, and vascular remodeling.
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References
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- Chatzizisis YS, Coskun AU, Jonas M, et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior J Am Coll Cardiol 2007;49:2379-2393.[Abstract/Free Full Text]
- Richter Y, Edelman ER. Cardiology is flow Circulation 2006;113:2679-2682.[Free Full Text]
- Stone PH, Coskun AU, Kinlay S, et al. Regions of low endothelial shear stress are sites where coronary plaque progress and vascular remodeling occurs in humans: an in-vivo serial study Eur Heart J 2007;28:705-710.[Abstract/Free Full Text]
- Wentzel JJ, Janssen E, Vos J, et al. Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling Circulation 2003;108:17-23.[Abstract/Free Full Text]
- Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions Arterioscler Thromb Vasc Biol 2000;20:1262-1275.[Free Full Text]
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