The effects of stenting on shear stress: Relevance to endothelial injury and repair

Biomedical Engineering, Department Cardiology, ErasmusMC, Rotterdam, The Netherlands.
Cardiovascular Research (Impact Factor: 5.94). 04/2013; 99(2). DOI: 10.1093/cvr/cvt090
Source: PubMed


Stent deployment following balloon angioplasty is used routinely to treat coronary artery disease (CAD). These interventions cause damage and loss of endothelial cells (EC), and thus promote in-stent thrombosis and restenosis. Injured arteries are repaired (intrinsically) by locally-derived EC and by circulating endothelial progenitor cells (EPC) which migrate and proliferate to re-populate denuded regions. However, re-endothelialisation is not always complete and often dysfunctional. Moreover, the molecular and biomechanical mechanisms that control EC repair and function in stented segments are poorly understood. Here we propose that stents modify endothelial repair processes, in part, by altering fluid shear stress, a mechanical force that influences EC migration and proliferation. A more detailed understanding of the biomechanical processes that control endothelial healing would provide a platform for the development of novel therapeutic approaches to minimise damage and promote vascular repair in stented arteries.

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Available from: Frank Gijsen, Sep 24, 2014
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    • "In vivo and in vitro studies have demonstrated that thicker struts were more thrombogenic than thinner struts, likely due to larger flow disturbances with thicker struts [11]. On the other hand, stent-induced mechanical injury of the endothelium is widely accepted as another mechanism that leads to stent thrombosis [6] [7]. Inhibited re-endothelialization, due to penetration of struts into the necrotic core of atherosclerotic plaque [9] or due to anti-proliferative drugs imparted by drug-eluting stents that aim to prevent in-stent restenosis (re-narrowing of the vessel), has also been linked to stent thrombosis [5]. "
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    ABSTRACT: Coronary stenting is one of the most commonly used approaches to open coronary arteries blocked due to atherosclerosis. However, stent struts can induce stent thrombosis due to altered hemodynamics and endothelial dysfunction, and the microscopic process is poorly understood. The objective of this study was to determine the microscale processes during the initiation of stent thrombosis.Methods We utilized a discrete element computational model to simulate the transport, collision, adhesion, and activation of thousands of individual platelets and red blood cells in thrombus formation around struts and dysfunctional endothelium.ResultsAs strut height increased, the area of endothelium activated by low shear stress increased, which increased the number of platelets in mural thrombi. These thrombi were generally outside regions of recirculation for shorter struts. For the tallest strut, wall shear stress was sufficiently low to activate the entire endothelium. With the entire endothelium activated by injury or denudation, the number of platelets in mural thrombi was largest for the shortest strut. The type of platelet activation (by high shear stress or contact with activated endothelium) did not greatly affect results.Conclusions During the initiation of stent thrombosis, platelets do not necessarily enter recirculation regions or deposit on endothelium near struts, as suggested by previous computational fluid dynamics simulations. Rather, platelets are more likely to deposit on activated endothelium outside recirculation regions and deposit directly on struts. Our study elucidated the effects of different mechanical factors on the roles of platelets and endothelium in stent thrombosis.
    Full-text · Article · Nov 2014 · Computers in Biology and Medicine
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    Preview · Article · Jun 2013 · Cardiovascular Research
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    ABSTRACT: Present study, for the first time, reports the development of a nanohybridized baculovirus based stent that can locally promote vascular re-endothelialization by efficient delivery of pro-angiogenic vascular endothelial growth factor (Vegf) genes. In vitro data demonstrated rapid expression of functionally active Vegf by the bioactive stent-transduced vascular cells. In vivo site-specific transgene expression was observed at the stented regions of balloon-denuded canine femoral artery, which eventually lead to significant endothelial recovery at the injured sites. A significant reduction in neointima formation (2.23 ± 0.56 mm(2) vs 2.78 ± 0.49 mm(2) and 3.11 ± 0.23 mm(2), p < 0.05; n = 8) and percent stenosis was observed in treated stent group compared to negative control and bare metal stent groups. These findings collectively implicate the potential of this newly developed baculovirus based biotherapeutic stent to ameliorate damaged vascular biology and attenuate re-narrowing of stented artery by inhibiting neointima formation.
    Full-text · Article · Aug 2013 · Scientific Reports
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