Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis?

Södergren, Anna; Karp, Kjell; Bengtsson, Christine; Möller, Bozena; Rantapää-Dahlqvist, Solbritt; Wållberg‐Jonsson, Solveig

doi:10.1155/2015/673018

Cited by 18 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Atherosclerosis is nowadays recognized as an inflammatory disease and there are many parallels between the pathological and immunological processes that occur in the synovium and the atheromatous lesions in the vessel walls [6]. A previous published study on the same individuals as in this study has suggested lipoprotein-associated phospholipase A2 (Lp-PLA2) as one of the biomarkers that might be able to indicate that, over time, the deleterious disease process in RA may also affect the vascular walls [16].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis

et al. 2019

Self Cite

View full text Add to dashboard Cite

Objectives Patients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease (CVD). In this prospective 5-year follow up of patients with RA, we analysed several biomarkers, known to be associated with atherosclerosis and/or inflammation in the general population. The aim of this study was to find out whether the RA-disease per se affect these biomarkers and if those could be associated with the progression of atherosclerosis, as measured by intima media thickness (IMT) among patients with early RA. Methods Patients from northern Sweden diagnosed with early RA, are consecutively recruited into an ongoing prospective study on CVD comorbidity. A subgroup of patients, aged ≤60 years (n = 71) was included for ultrasound measurements of IMT at inclusion (T0) and after 5 years (T5) together with age-sex-matched controls (n = 40). The patients were clinically assessed. Blood was analysed for lipids, ESR and CRP and several biomarkers known to be associated with atherosclerosis in the general population. Results At T0, the patients with RA had significantly lower levels of MIF and significantly higher levels of interleukin (IL)-18 and MIC-1 compared with controls. At T5, the patients with RA had significantly higher levels of pentraxin3, MIC-1, TNF-R2, ICAM-1, VCAM-1 and endostatin compared with controls. At T0 the levels of MPO correlated with DAS28, sCD40L with CRP and IL-18 with systolic blood pressure and Reynolds risk score. Using PLSR on a CVD-panel analysed with multiplex immunoassay, the patients with RA could be correctly classified into those who had a worsening in their IMT over the five years or not. Here, MMP3 was identified as influential. Conclusions This study indicates that the RA disease itself could affect several of the biomarkers in this study, and possibly also the processes involved in the development of atherosclerosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In organisms, there are more than 14 different species of PLA 2 enzymes, which may play different or similar roles in many biological processes. Among these 14 isoforms, four main subtypes of PLA 2 include the cytosolic phospholipase A 2 (cPLA 2 ), calcium-independent phospholipase A 2 (iPLA 2 ), secreted phospholipase A 2 (sPLA 2 ), and the platelet activating factor acetyl hydrolase/oxidized lipid lipoprotein-associated phospholipase A 2 (LpPLA 2 ) are widely studied and identified by researchers ( Kozaki et al, 2015 ; Sodergren et al, 2015 ). cPLA 2 is one of the main subtypes produced in the inflammation area and also the only one PLA 2 with a catalyzed-hydrolysis peculiarity for arachidonic acid (AA) at the position of sn-2 in phospholipids ( Hartz et al, 2019 ).…”

Section: Therapeutic Enzymes and Their Derivatives In Ramentioning

confidence: 99%

Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal Products in Rheumatoid Arthritis

Cai

Han

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) acts as one of the most common, agnogenic and chronic inflammatory-autoimmune disorder which is characterized by persistent synovitis, cartilage destruction, and joint deformities, leads to a wide range of disabilities, and increased mortality, thus imposing enormous burdens. Several drugs with anti-inflammatory and immunomodulatory properties such as celecoxib, diclofenac and methotrexate are being selected as conventional drugs in the allopathic system of medicine for the treatment of RA in clinic. However, there are some serious side effects more or less when using these drugs because of their short poor bioavailability and biological half-life for a long time. These shortcomings greatly promote the exploration and application of new low- or no-toxicity drugs for treating the RA. Meanwhile, a growing number of studies demonstrate that several herbs present certain anti-inflammatory and anti-arthritic activities through different enzymes and their derivatives, which indicate that they are promising therapeutic strategies when targeting these mediators based on herbal medicinal products in RA research. This review article summarizes the roles of the main enzymes and their derivatives during the pathogenesis of RA, and clearly clarifies the explicit and potential targeted actions of herbal medicinal products that have anti-RA activity. Our review provides timely and critical reference for the scientific rationale use of herbal medicinal products, with the increasing basic research and clinical application of herbal medicinal products by patients with RA.

show abstract

“…In a cohort of rheumatoid arthritis (RA) patients, the baseline Lp‐PLA2 mass was significantly associated with both disease severity and subclinical atherosclerosis including IMT and flow‐mediated dilation at both baseline and follow‐up. Consequently, Lp‐PLA2 might be a biomarker of vascular damage among patients with RA . In addition, a prospective longitudinal cohort study identified the plasma Lp‐PLA2 activity and mass, which were independently and significantly associated with incident abdominal aortic aneurysm (AAA), as markers of AAA risk …”

Section: Biological Functions and Disease Implicationsmentioning

confidence: 99%

“…Consequently, Lp-PLA2 might be a biomarker of vascular damage among patients with RA. 232 In addition, a prospective longitudinal cohort study identified the plasma Lp-PLA2 activity and mass, which were independently and significantly associated with incident abdominal aortic aneurysm (AAA), as markers of AAA risk. 17 Certain relationships between Lp-PLA2 and these diseases were already detected; however, further research is needed for a deeper understanding of the associations.…”

mentioning

confidence: 99%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

Medicinal Research Reviews

131

140

View full text Add to dashboard Cite

Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.

show abstract

Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis?

Cited by 18 publications

References 37 publications

Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis

Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis

Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal Products in Rheumatoid Arthritis

Lipoprotein‐associated phospholipase A2: The story continues

Contact Info

Product

Resources

About