The amount of fibrinogen-positive platelets predicts the occurrence of in-stent restenosis

Jaster, Markus; Horstkotte, Dieter; Willich, Tobias; Stellbaum, Caroline; Knie, Wulf; Spencker, Sebastian; Pauschinger, M.; Schultheiss, Heinz‐Peter; Rauch, Ursula

doi:10.1016/j.atherosclerosis.2007.03.020

Cited by 15 publications

(9 citation statements)

References 28 publications

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“…Previous work in the field has demonstrated a therapeutic value of strategies based on systemic or local attenuation of neutrophils [10, 29] and macrophages [30, 31], the main cell types mediating acute and chronic phases of inflammatory response, respectively. Additionally, elevated platelet count and function are also recognized ISR risk factors [32, 33]. A non-occluding thrombus formed over the stent struts immediately after stent implantation serves as a nidus for SMC migrating from the media in response to gradient of platelet-secreted growth factors, mainly PDGF BB.…”

Section: Discussionmentioning

confidence: 99%

Enhanced biocompatibility of CD47-functionalized vascular stents

et al. 2016

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The effectiveness of endovascular stents is hindered by in-stent restenosis (ISR), a secondary re-obstruction of treated arteries due to unresolved inflammation and activation of smooth muscle cells in the arterial wall. We previously demonstrated that immobilized CD47, a ubiquitously expressed transmembrane protein with an established role in immune evasion, can confer biocompatibility when appended to polymeric surfaces. In present studies, we test the hypothesis that CD47 immobilized onto metallic surfaces of stents can effectively inhibit the inflammatory response thus mitigating ISR. Recombinant CD47 (recCD47) or a peptide sequence corresponding to the Ig domain of CD47 (pepCD47), were attached to the surfaces of both 316L-grade stainless steel foils and stents using bisphosphonate coordination chemistry and thiol-based conjugation reactions to assess the anti-inflammatory properties of CD47-functionalized surfaces. Initial in vitro and ex vivo analysis demonstrated that both recCD47 and pepCD47 significantly reduced inflammatory cell attachment to steel surfaces without impeding on endothelial cell retention and expansion. Using a rat carotid stent model, we showed that pepCD47-functionalized stents prevented fibrin and platelet thrombus deposition, inhibited inflammatory cell attachment, and reduced restenosis by 30%. It is concluded that CD47-modified stent surfaces mitigate platelet and inflammatory cell attachment, thereby disrupting ISR pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Enhanced biocompatibility of CD47-functionalized vascular stents

et al. 2016

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“…Nonetheless, the fact that we found elevated levels of both fibrinogen protein and its mRNA suggests that fibrinogen in the aged vasculature may come from platelets. Interestingly, the number of fibrinogen-positive platelets predicts restenosis after stent implantation in acute myocardial infarction patients (20). Furthermore, it is known that platelets accumulate intracellular fibrinogen with age (17) and that increased fibrinogen concentration is significantly associated with the risk of vascular proliferative diseases (47).…”

Section: Discussionmentioning

confidence: 99%

Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

Rodriguez-Menocal

Faridi

Martinez

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Padron RI. Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling. Am J Physiol Heart Circ Physiol 306: H641-H653, 2014. First published January 10, 2014; doi:10.1152/ajpheart.00641.2013.-Aging has been associated with pathological vascular remodeling and increased neointimal hyperplasia. The understanding of how aging exacerbates this process is fundamental to prevent cardiovascular complications in the elderly. This study proposes a mechanism by which aging sustains leukocyte adhesion, vascular inflammation, and increased neointimal thickness after injury. The effect of aging on vascular remodeling was assessed in the rat balloon injury model using microarray analysis, immunohistochemistry, and LINCOplex assays. The injured arteries in aging rats developed thicker neointimas than those in younger animals, and this significantly correlated with a higher number of tissue macrophages and increased vascular IL-18. Indeed, IL-18 was 23-fold more abundant in the injured vasculature of aged animals compared with young rats, while circulating levels were similar in both groups of animals. The depletion of macrophages in aged rats with clodronate liposomes ameliorated vascular accumulation of IL-18 and significantly decreased neointimal formation. IL-18 was found to inhibit apoptosis of vascular smooth muscle cells (VSMC) and macrophages, thus favoring both the formation and inflammation of the neointima. In addition, injured arteries of aged rats accumulated 18-fold more fibrinogen-␥ than those of young animals. Incubation of rat peritoneal macrophages with immobilized IL-18 increased leukocyte adhesion to fibrinogen and suggested a proinflammatory positive feedback loop among macrophages, VSMC, and the deposition of fibrinogen during neointimal hyperplasia. In conclusion, our data reveal that concentration changes in vascular cytokine and fibrinogen following injury in aging rats contribute to local inflammation and postinjury neointima formation. inflammation; vascular injury; aging; neointima; vascular smooth muscle cells AGING IS RECOGNIZED AS A MAJOR and independent risk factor for the development of vascular restenosis (29). This risk can be explained by profound, age-dependent changes in vascular structure and physiology that lead to endothelial dysfunction (18) and a chronic inflammatory stage (53), which impair healing and render a vascular system prone to develop occlusive neointimas in response to injury. However, even when this notion is largely accepted, the mechanisms by which aging alters vascular physiology and repair have remained understudied to date.The process of aging increases and sustains inflammation within the vascular wall (52). Macrophages are commonly recognized as the most important cell type in the chronicity of this process (37). Indeed, inflammation in arteries of aged individuals is evidenced by an excessive accumulation of macrophages in the inner layer of the arterial wall (intima), and this occurs in the presence o...

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“…Furthermore the increase of platelet-mediated thrombin around the deployed stent can stimulate the migration and proliferation of vascular smooth muscle cells, which positively influence the development of restenosis. Recently, a clinical trial by Jaster et al (2008) had demonstrated that the indicators of platelet activation could be used to pre-indicate the degree of restenosis. The GP IIb/ IIIa can block the glycoprotein IIb/IIIa receptors on platelets, preventing the formation of fibrinogen bridges, the final common pathway in platelet thrombus formation.…”

Section: Discussionmentioning

confidence: 99%

Ultrasonic atomization and subsequent desolvation for monoclonal antibody (mAb) to the glycoprotein (GP) IIIa receptor into drug eluting stent

Wang¹,

Luo²,

Yin³

et al. 2010

Journal of Microencapsulation

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An eluting-stent system with mAb dispersed in the PLLA (poly (L-lactic acid)) was validated in vitro. Specifically designed spray equipment based on the principle of ultrasonic atomization was used to produce a thin continuous PLLA (poly (L-lactic acid)) polymer coating incorporating monoclonal antibody (mAb). This PLLA coating was observed in light microscopy (LM) and scanning electron microscopy (SEM). The concentration of the monoclonal antibody (mAb) to the platelet glycoprotein (GP) IIIa receptor and the eluting rate were then measured by a radioisotope technique with (125)I-labelled GP IIIa mAb. An in vitro perfusion circuit was designed to evaluate the release rates at different velocities (10 or 20 ml min(-1)). The PLLA coating was thin and transparent, uniformly distributed on the surface of the stent. Three factors influenced its thickness: PLLA concentration, duration and gas pressure. The concentration of mAb was influenced by the duration of absorption and the concentration of the mAb solution; the maximum was 1662.23 + or - 38.83 ng. The eluting rate was fast for the first 2 h, then decreased slowly and attained 80% after 2 weeks. This ultrasonic atomization spray equipment and technological process to prepare protein eluting-stents were proved to be effective and reliable.

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The amount of fibrinogen-positive platelets predicts the occurrence of in-stent restenosis

Cited by 15 publications

References 28 publications

Enhanced biocompatibility of CD47-functionalized vascular stents

Enhanced biocompatibility of CD47-functionalized vascular stents

Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

Ultrasonic atomization and subsequent desolvation for monoclonal antibody (mAb) to the glycoprotein (GP) IIIa receptor into drug eluting stent

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