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- Holsti, Mari, 1963-, et al.
(författare)
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Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 56:1, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. Methods: This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta <= 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA >= 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Results: Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Conclusion: Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall.
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- Holsti, Mari, 1963-
(författare)
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Vascular remodelling and circulating basement membrane fragments in abdominal aortic aneurysm
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An abdominal aortic aneurysm (AAA) is a degenerative disease, characterized by advanced inflammation and extracellular matrix (ECM) remodelling. Enhanced protease activity mediated by cytokines results in the degradation of ECM proteins, leading to the generation of different bioactive fragments. Some of these generated fragments are released from the vascular basement membrane (VBM), a highly specialized ECM. VBM provides mechanical and structural stability and regulates many important cellular functions of the vascular system. Type IV and XVIII collagens are two structural proteins in VBM, with crucial roles in maintaining of the VBM integrity and vascular architecture. Circulating levels of type IV and XVIII collagen fragments are found physiologically, but have also been associated with many diseases. Remodelling of VBM and expression of its components has not been as well studied in AAA as that of the interstitial ECM.Here we investigate these VBM collagens, their expression and possible association with aortic diameter and expansion rate in individuals with an AAA in comparison with different control groups. Further we study whether there is a link between the circulating VBM collagen fragments and several inflammatory markers, all highly involved in AAA pathogenesis. Lastly, we study the impact of surgical intervention on plasma levels of VBM collagens in patients treated by either open surgical repair (OSR) or endovascular aortic aneurysm repair (EVAR).Methods: Circulating levels of type IV and XVIII collagen fragments were analysed in individuals with an AAA and compared with healthy controls and patients with peripheral artery disease (paper I). A possible association between VBM collagen fragments and the aortic diameter and expansion was studied in a large population-based cohort of 615 men stratified into three aortic diameter groups based on initial maximum aortic diameter (paper II). Furthermore, 159 individuals were followed up over time with repeated measurements of aortic diameter and blood samples. The follow up cohort were divided into two subgroups based on expansion rate of AAA. Moreover, the location of VBM collagens in tissue from aortic wall in individuals with an AAA was characterized and the expression pattern was compared with normal aorta (paper II). In paper III, the association between the plasma levels of VBM collagens and inflammatory markers; IL-1 (IL-1α and IL-1β), IL-6, IL-8, TNF-α INF-γ and hs-CRP were studied in same cohort as paper II. Finally, the effect of surgical intervention on circulating levels of VBM collagen fragments was investigated in AAA patients who had undegone either OSR or EVAR by comparison of plasma levels before and after AAA repair.Ultrasound technique was used for measurements of aortic diameter (paper I, II, III and IV). Analysis of circulating VBM collagens and inflammatory markers were performed by ELISA-assay (Paper I, II, III and IV) and Multiplex-assays, respectively (paper III). Aortic wall tissues were analysed by haematoxylin and eosin (H&E) and immunofluorescence staining (Paper II).Results: There were significantly increased plasma levels of VBM collagen fragments in individuals with an AAA, compared with healthy controls and individulas with a peripheral artery disease (PAD), (Paper I). The levels of type IV collagen in AAA patients did not differ from the group with PAD, and there were no significant differences between the control groups regarding plasma levels of both VBM collagen fragments (Paper I). The increased levels of VBM collagen fragments were significantly associated with aortic diameter with highest levels in the group with an AAA (Paper II). Altered expression of the VBM collagens and fragmentation of elastic fibres were observed in tissue from AAA patients (Paper II). A significant association between the levels of pro-inflammatory cytokines IL-6 and IL-8, and VBM collagens was found. Additionally, there were a significant association between the plasma levels of IL-8, TNF-α and hs-CRP and an AAA (Paper III). Aneurysms with faster expansion rate had significantly higher levels of IL-6, IL-1β, and type XVIII/endostatin collagen. Additionally, IL-6, type XVIII/endostatin collagen and baseline-aortic diameter were significantly associated with expansion rate (Paper III). AAA repair was associated with changes in plasma levels of VBM collagens (Paper IV).Conclusion: Circulating levels of VBM collagens were increased in patients with an AAA, and significantly associated with aortic diameter and expansion rate. The expression of VBM collagens was altered in AAA tissue compared with normal aorta. In addition, plasma levels of several inflammatory markers were associated as with VBM collagens, aortic diameter and expansion rate. The levels of both VBM collagens were altered at short and long time after AAA repair.
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- Sörelius, Karl, 1981-, et al.
(författare)
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Nationwide Study on Treatment of Mycotic Thoracic Aortic Aneurysms
- 2019
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 57:2, s. 239-246
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Mycotic aortic aneurysms are rare, life threatening, and complex. This nationwide study aimed to assess outcome after repair of mycotic thoracic aortic aneurysms (MTAAs). Methods: Patients treated in Sweden for MTAAs between 2000 and 2016 were identified in the Swedish vascular registry (2010-16) and local patient registries (2000-09). Primary outcome was survival, and secondary outcomes included surgical strategy, rate of infection related complications (IRC), and re-operations. Results: Fifty-two patients (median age 71 +/- 8.1 years; 28 [54%] men, 13 [25%] ruptured) were identified (3.6% of all thoracic aortic aneurysm repairs in Sweden). Aneurysm location was aortic arch (n = 6; 11%), descending aorta (n = 42; 81%), and multiple locations (n = 4; 8%). Twenty-nine (56%) patients had positive cultures; the most prevalent agent was Staphylococcus aureus (n = 16; 31%). Operative techniques included thoracic endovascular aortic repair (TEVAR; n = 35 [67%]), fenestrated/branched TEVAR (n = 8; 15%), hybrid repair (n = 7; 14%), and open patch repair (n = 2; 4%). Survival was 92% (95% confidence interval [CI] 88-96) at 30 days, 88% (95% CI 84-93) at three months, 78% (73-84) at one year, and 71% (64-77) at five years. The mean follow up among survivors (> 90 days) was 45 months (range 4-216 months). Antibiotics were administered for a median of 15 weeks (range 0-220 weeks). IRCs occurred in nine patients (17%): sepsis (n = 3), graft infection (n = 3), recurrent mycotic aneurysm (n = 1), aorto-oesophageal/bronchial fistula (n = 2). Six (67%) IRCs were fatal; 80% occurred within the first year. Re-operations were performed in nine patients (17%). Conclusions: TEVAR was often used as treatment for MTAAs, with acceptable short- and long-term survival when compared with open cohorts in the literature. IRCs are of concern and warrant follow up and long-term antibiotic treatment.
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