Dataset Information

Oxidized Lipids and Lipoprotein Dysfunction in Psoriasis.

ABSTRACT:

Background

Psoriasis is a chronic immune-mediated inflammatory skin disease associated with increased development of metabolic abnormalities including obesity and dyslipidemia, as well as increased cardiovascular disease (CVD) risk. Shared pathophysiological mechanisms linking psoriasis to CVD include altered immune activation, elevated chronic systemic inflammation, and lipoprotein dysfunction characterized by oxidative damage to lipids and apolipoproteins.

Objective

This review aims to provide evidence-based proof for existing relationships between psoriatic inflammation, lipid oxidation, and increased CVD risk.

Methods

We included review articles and original research papers, published between 1980 and 2020, using the following key words: psoriasis, oxidized lipids, oxidation, dyslipidemia, and inflammation.

Results

Systemic inflammation underlying psoriasis leads to increased skin accumulation of pro-inflammatory oxidized lipids, derived from the omega-6 fatty acids, along with counteracting anti-inflammatory lipid mediators, products of the omega-3 polyunsaturated fatty acids. Imbalance in these metabolites culminates in impaired inflammation resolution and results in multisystemic biological alterations. Sustained systemic inflammation results in excessive lipid oxidation, generating proatherogenic oxidized low- and high-density lipoproteins. Together, these pathophysiological mechanisms contribute to increased CVD risk associated with psoriasis disease.

Conclusion

Available anti-inflammatory treatment showed promising clinical results in treating psoriasis, although further research is warranted on managing associated dyslipidemia and establishing novel cardiometabolic markers specific for both skin and vascular pathology.

SUBMITTER: Sorokin AV

PROVIDER: S-EPMC7646705 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Oxidized Lipids and Lipoprotein Dysfunction in Psoriasis.

Sorokin Alexander V AV Remaley Alan T AT Mehta Nehal N NN

Journal of psoriasis and psoriatic arthritis 20200826 4

<h4>Background</h4>Psoriasis is a chronic immune-mediated inflammatory skin disease associated with increased development of metabolic abnormalities including obesity and dyslipidemia, as well as increased cardiovascular disease (CVD) risk. Shared pathophysiological mechanisms linking psoriasis to CVD include altered immune activation, elevated chronic systemic inflammation, and lipoprotein dysfunction characterized by oxidative damage to lipids and apolipoproteins.<h4>Objective</h4>This review ...[more]

PMID: 33163854

Similar Datasets

Project description:Background and aimsAs the incidence of nonalcoholic steatohepatitis (NASH) continues to rise, understanding how normal liver functions are affected during disease is required before developing novel therapeutics which could reduce morbidity and mortality. However, very little is understood about how the transport of proteins and cells from the liver by the lymphatic vasculature is affected by inflammatory mediators or during disease.MethodsTo answer these questions, we utilized a well-validated mouse model of NASH and exposure to highly oxidized low density lipoprotein (oxLDL). In addition to single cell sequencing, multiplexed immunofluorescence and metabolomic analysis of liver lymphatic endothelial cells (LEC)s we evaluated lymphatic permeability and transport both in vitro and in vivo.ResultsConfirming similarities between human and mouse liver lymphatic vasculature in NASH, we found that the lymphatic vasculature expands as disease progresses and results in the downregulation of genes important to lymphatic identity and function. We also demonstrate, in mice with NASH, that fluorescein isothiocyanate (FITC) dextran does not accumulate in the liver draining lymph node upon intrahepatic injection, a defect that was rescued with therapeutic administration of the lymphatic growth factor, recombinant vascular endothelial growth factor C (rVEGFC). Similarly, exposure to oxLDL reduced the amount of FITC-dextran in the portal draining lymph node and through an LEC monolayer. We provide evidence that the mechanism by which oxLDL impacts lymphatic permeability is via a reduction in Prox1 expression which decreases lymphatic specific gene expression, impedes LEC metabolism and reorganizes the highly permeable lymphatic cell-cell junctions which are a defining feature of lymphatic capillaries.ConclusionsWe identify oxLDL as a major contributor to decreased lymphatic permeability in the liver, a change which is consistent with decreased protein homeostasis and increased inflammation during chronic liver disease.

Project description:Importance:Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. Objective:To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. Design, Setting, and Participants:In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. Exposures:Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. Main Outcomes and Measures:Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. Results:Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P?<?.001), and were associated with Psoriasis Area Severity Index (PASI) score (??=?0.23; 95% CI, 0.082-0.374; P?=?.003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (??=?0.11; 95% CI, 0.016-0.200; P?=?.023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (??=?0.10; 95% CI, 0.014-0.193; P?=?.03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P?=?.01) was associated with a reduction in NCB (??=?0.14; 95% CI, 0.028-0.246; P?=?.02). Conclusions and Relevance:Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.

Dataset Information

Oxidized Lipids and Lipoprotein Dysfunction in Psoriasis.

Background

Objective

Methods

Results

Conclusion

Publications

Oxidized Lipids and Lipoprotein Dysfunction in Psoriasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets