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- D'Ascenzo, Fabrizio, et al.
(author)
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Incidence and predictors of coronary stent thrombosis : Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses
- 2013
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 575-584
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Journal article (peer-reviewed)abstract
- BACKGROUND:Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis.METHODS: PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥2000 patients undergoing stenting or reporting on ≥25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised.RESULTS:A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently.CONCLUSIONS:Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.
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| 2. |
- Tykesson, Emil, et al.
(author)
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Dermatan sulfate epimerase 1 and dermatan 4-O-sulfotransferase 1 form complexes that generate long epimerized 4-O-sulfated blocks
- 2018
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In: Journal of Biological Chemistry. - 0021-9258. ; 293:35, s. 13725-13735
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Journal article (peer-reviewed)abstract
- During the biosynthesis of chondroitin/dermatan sulfate (CS/ DS), a variable fraction of glucuronic acid is converted to iduronic acid through the activities of two epimerases, dermatan sulfate epimerases 1 (DS-epi1) and 2 (DS-epi2). Previous in vitro studies indicated that without association with other enzymes, DS-epi1 activity produces structures that have only a few adjacent iduronic acid units. In vivo, concomitant with epimerization, dermatan 4-O-sulfotransferase 1 (D4ST1) sulfates the GalNAc adjacent to iduronic acid. This sulfation facilitates DS-epi1 activity and enables the formation of long blocks of sulfated iduronic acid– containing domains, which can be major components of CS/DS. In this report, we used recombinant enzymes to confirm the concerted action of DS-epi1 and D4ST1. Confocal microscopy revealed that these two enzymes colocalize to the Golgi, and FRET experiments indicated that they physically interact. Furthermore, FRET, immunoprecipitation, and cross-linking experiments also revealed that DS-epi1, DS-epi2, and D4ST1 form homomers and are all part of a hetero-oligomeric complex where D4ST1 directly interacts with DS-epi1, but not with DS-epi2. The cooperation of DS-epi1 with D4ST1 may therefore explain the processive mode of the formation of iduronic acid blocks. In conclusion, the iduronic acid–forming enzymes operate in complexes, similar to other enzymes active in glycosaminoglycan biosynthesis. This knowledge shed light on regulatory mechanisms controlling the biosynthesis of the structurally diverse CS/DS molecule.
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