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- Annema, W, et al.
(författare)
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Group IIA Secretory Phospholipase A2 Predicts Graft Failure and Mortality in Renal Transplant Recipients by Mediating Decreased Kidney Function
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- The acute phase protein group IIA secretory phospholipase A2 (sPLA2-IIA) has intrinsic proatherosclerotic properties. The present prospective cohort study investigated whether plasma sPLA2-IIA associates with graft failure, cardiovascular, and all-cause mortality in renal transplant recipients (RTRs), patients with accelerated atherosclerosis formation both systemically and within the graft. In 511 RTRs from a single academic center with stable graft function >1 year, baseline plasma sPLA2-IIA was determined by ELISA. Primary end points were death-censored graft failure and mortality (median follow-up, 7.0 years). Baseline sPLA2-IIA was higher in RTRs than in healthy controls (median 384 ng/dL (range 86–6951) vs. 185 ng/dL (range 104–271), p < 0.001). Kaplan–Meier analysis demonstrated increased risk for graft failure (p = 0.002), as well as cardiovascular (p < 0.001) and all-cause mortality (p < 0.001), with increasing sPLA2-IIA quartiles. Cox regression showed strong associations of sPLA2-IIA with increased risks of graft failure (hazard ratio (HR) = 1.42 (1.11–1.83), p = 0.006), as well as cardiovascular (HR = 1.48 (1.18−1.85), p = 0.001) and all-cause mortality (HR = 1.39 (1.17−1.64), p < 0.001), dependent on parameters of kidney function. Renal function during follow-up declined faster in RTRs with higher baseline sPLA2-IIA levels. In RTRs, sPLA2-IIA is a significant predictive biomarker for chronic graft failure, as well as overall and cardiovascular disease mortality dependent on kidney function. This dependency is conceivably explained by sPLA2-IIA impacting negatively on kidney function.
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| 8. |
- Orthofer, M, et al.
(författare)
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Identification of ALK in Thinness
- 2020
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 181:6, s. 1246-
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Vlacil, AK, et al.
(författare)
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Deficiency of Nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 reduces atherosclerosis
- 2020
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Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 115:4, s. 47-
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is crucially fueled by inflammatory pathways including pattern recognition receptor (PRR)-related signaling of the innate immune system. Currently, the impact of the cytoplasmic PRRs nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2 is incompletely characterized. We, therefore, generated Nod1/Nod2 double knockout mice on a low-density lipoprotein receptor (Ldlr)-deficient background (= Ldlr−/−Nod1/2−/−) which were subsequently analyzed regarding experimental atherosclerosis, lipid metabolism, insulin resistance and gut microbiota composition. Compared to Ldlr−/− mice, Ldlr−/−Nod1/2−/− mice showed reduced plasma lipids and increased hepatic expression of the scavenger receptor LDL receptor-related protein 1 after feeding a high-fat diet for 12 weeks. Furthermore, intestinal cholesterol and its bacterial degradation product coprostanol were elevated in Ldlr−/−Nod1/2−/− mice, correlating with the increased abundance of Eubacterium coprostanoligenes as assessed by 3rd generation sequencing of the gut microbiota. Atherosclerotic plaques of Ldlr−/−Nod1/2−/− mice exhibited less lipid deposition and macrophage accumulation. Moreover, macrophages from Ldlr−/−Nod1/2−/− mice showed higher expression of the cholesterol efflux transporters Abca1 and Abcg1 and accordingly reduced foam cell formation. Deficiency of Nod1 and Nod2 led to reduced plaque lipid deposition and inflammatory cell infiltration in atherosclerotic plaques. This might be explained by diminished plasma lipid levels and foam cell formation due to altered expression of key regulators of the hepatic cholesterol pathway as well as differential intestinal cholesterol metabolism and microbiota composition.
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