Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients

Rolla, Roberta; Mauri, Andreana De; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

doi:10.1007/s40620-015-0194-0

Cited by 12 publications

(8 citation statements)

References 35 publications

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“…Rutin inhibited phospholipase A2 (PLA2) in rats (membrane‐associated PLA2 in lungs) and humans (synovial fluid‐derived and non‐pancreatic PLA2) . PLA2 activates pro‐inflammatory cytokines involved in inflammation and progression of disease in CKD patients on dialysis . PLA2 produces cytokines that can cause tubular injury and induce reactive oxygen species that provoke inflammation .…”

Section: Can This Adenine Model Be Used To Test Therapeutic Interventmentioning

confidence: 99%

Adenine‐induced chronic kidney disease in rats

2017

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Section: Can This Adenine Model Be Used To Test Therapeutic Interventmentioning

confidence: 99%

Adenine‐induced chronic kidney disease in rats

2017

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“…Therefore, Lp-PLA2 was suggested to be a risk , correlating with the severity of atherosclerosis in patients with carotid artery disease [22] . Rolla et al [23] contributed to that issue by demonstrating in their prospective trial that HD patients with an Lp-PLA2 plasma activity >194 nmol/ min/mL experienced more CVEs compared to patients with lower levels. In our study, we also measured elevated Lp-PLA2 plasma activity levels in atherosclerosis-prone CKD5-D patients (A+) compared to those without atherosclerosis (A-), although the absolute Lp-PLA2 activity values determined in both studies were quite different.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Lipoprotein-Associated Phospholipase A2 in Monocyte Subsets: Impact of Uremia and Atherosclerosis

Ulrich

Trojanowicz

Fiedler

et al. 2016

Nephron

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Background: Monocytic products, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), may participate in the development of atherosclerosis. Heterogeneity of monocytes is widely acknowledged. Classical, intermediate, and non-classical subsets can be discerned. Recently, an inflammatory, pro-atherogenic monocyte population could be identified in hemodialysis patients. In this study, we investigated the expression of Lp-PLA2 on leucocytes and different monocyte subpopulations and their possible role in uremia, inflammation, and atherosclerosis. Methods: Chronic kidney disease stage 5-D (CKD5-D; n = 57), healthy control subjects with hs-C-reactive protein (CRP) levels ≤1 mg/L (CO-N, n = 22) and a control group with inflammatory activation (CRP levels >1 mg/L, CO-I, n = 29) were enrolled in this cross-sectional observation. The CKD5-D cohort was dichotomized into patients with (A+) and without subclinical atherosclerosis (A-) by carotid artery ultrasound measurement. Lp-PLA2 activity was determined in plasma samples, Lp-PLA2 mRNA expression analysis in leucocytes, and sorted monocyte subsets. Effects of Lp-PLA2 overexpression were studied in classical vs. intermediate and non-classical subsets. Results: The classical monocytes expressed the highest Lp-PLA2 mRNA levels as compared to other subpopulations. CKD5-D patients revealed significantly higher Lp-PLA2 transcripts, as well as higher Lp-PLA2 plasma activity as compared to healthy and “inflammatory” controls. In vitro data confirmed that uremia significantly contributes to Lp-PLA2 mRNA upregulation. Non-classical monocytes of A+ patients revealed significant higher Lp-PLA2 mRNA compared to A-. Conclusion: Uremic environment but not inflammation per se increases plasma Lp-PLA2 activity and upregulates monocytic Lp-PLA2 mRNA expression. The highest Lp-PLA2 levels were found in the classical and not in the inflammatory subsets. Atherosclerosis also contributes to a subset-specific increase in Lp-PLA2 mRNA expression.

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“…The proof of this phenomenon is found in evidence of elevated levels of peripheral markers of immune activation (e.g., cytokines and chemokines) [25,26,27,28,29,30,31,32]. Other proinflammatory cell products, like NGAL [13], galectin-3 (GAL-3) [33,] and Lp-PLA 2 [34], the first released by polymorphonuclear leukocytes and the others by macrophages, have been shown to be augmented as well.…”

Section: Adaptive and Innate Immunity Abnormalities In Esrdmentioning

confidence: 99%

“…In patients with ESRD, several mediators of inflammation share a link with cardiovascular disease [34,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63] (Table 1). Indeed, this is quite dubious for C reactive protein (CRP), either in terms of mere association or from a pathogenic perspective.…”

Section: Mechanisms By Which Inflammation May Increase Cardiovascularmentioning

confidence: 99%

“…In fact, while in some trials CRP did not merge as a strong independent cardiovascular risk factor (instead of IL-1, IL-6, TNF-α, albumin, and body mass index) [52,53,55,60], the genetic analysis of polymorphisms leading to a gain of function of gene transcription of CRP failed to demonstrate a dose-dependent effect of this marker [64] and a possible causal role. Other biomarkers (sTWEAK, MIC-1, CD4 + CD28-null T-cells, RANKL, pentraxin3, CCR5, GAL-3, myeloperoxidase, Lp-PLA 2 , and sCD14) , have also been linked to cardiovascular risk in ESRD [32,34,45,46,47,48,51,57,61,62,63]. Besides studies of association, there are evidences that uremic serum directly causes vascular damage [65] via activation of pro-inflammatory endothelial pathways (e.g., TLR4, NF-κB, NALP3 [NACHT, LRR and PYD domains-containing protein 3] and p38 MAPK [p38 mitogen-activated protein kinase]), which induce increased endothelial expression of ICAM-1, VCAM-1 (vascular cell adhesion molecule-1), von Willebrand factor [66,67], reduced nitric oxide availability, generating endothelial dysfunction [68].…”

Section: Mechanisms By Which Inflammation May Increase Cardiovascularmentioning

confidence: 99%

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Targeting Immunity in End-Stage Renal Disease

2017

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Background: Despite the stable incidence of end-stage renal disease (ESRD), it continues to be associated with an unacceptably high cardiovascular risk. Summary: ESRD is characterized by enhanced oxidative stress and severe inflammation, which boost cardiovascular risk, thus increasing cardiovascular-associated mortality rate. While substantial effort has been made in the technological innovation of dialytic techniques, few significant advances have been made to reduce inflammation in patients with ESRD. Indeed, this contrasts with the extensive scientific breakthroughs made in the basic field of science in targeting inflammation. There is thus a pressing need for clinical trials to test the effect of reducing inflammation in patients with ESRD. Here, we will revisit the negative effect of ESRD on inflammation and explore the impact of enhanced inflammation on cardiovascular outcomes and survival in patients with ESRD. Finally, we will discuss the need for clinical trials that target inflammation in ESRD, as well as weigh potential disadvantages and offer novel innovative approaches. Key Message: We will try to understand why the issue of inflammation has not been successfully addressed thus far in patients with ESRD, while at the same time weighing the potential disadvantages and offering novel innovative approaches for targeting inflammation in patients with ESRD.

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Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients

Abstract: Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

Cited by 12 publications

References 35 publications

Adenine‐induced chronic kidney disease in rats

Adenine‐induced chronic kidney disease in rats

Differential Expression of Lipoprotein-Associated Phospholipase A2 in Monocyte Subsets: Impact of Uremia and Atherosclerosis

Targeting Immunity in End-Stage Renal Disease

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