Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease

Abstract

Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases.

Evaluation of dysfunctional high‐density lipoprotein levels with myeloperoxidase/paraoxonase‐1 ratio in rheumatoid arthritis

“…Furthermore, PON1 levels negatively correlated with DAS28 scores. Parada‐Turska et al showed that both activity and level of PON1 were decreased in RA patients and these decrease associated with disease activity 28 . Besides, decreased PON1 levels have also been shown to be associated with increased CVD 29 .…”

“…Parada-Turska et al showed that both activity and level of PON1 were decreased in RA patients and these decrease associated with disease activity. 28 Besides, decreased PON1 levels have also been shown to be associated with increased CVD. 29 Shevchuk et al demonstrated that the PON1 activity in RA patients is associated with several CVD diseases such as atherosclerotic vascular damage and myocardial hypertrophy.…”

Cardiovascular Disease and Chronic Endodontic Infection. Is There an Association? A Systematic Review and Meta-Analysis

“…To this end, it has been suggested that various factors might be implicated in the pathogenic mechanisms of such a condition, including underlying grounds of diabetes mellitus and rheumatoid arthritis [46]. An important consideration when evaluating the onset of CVDs is the close investigation of other entities that may run ahead and parallel with the CVDs and are effectively served by inflammation, tissue damage, and macrovascular circulation-related issues [47,48]. The results include the development of atheromatosis or atherosclerosis, carotid plaque, and luminal narrowing of arteries [49], with most severe endpoints being stroke, myocardial infraction, and mortality.…”

The Causal relationship of adipokines with rheumatoid arthritis among European populations: a two-sample Mendelian randomization study

“…Author details 1 The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China. 2 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. 3 The Second A liated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China.…”

“…Rheumatoid arthritis (RA) is a common and chronic autoimmune disease, characterized by synovial in ammation, pannus formation and joint destruction, eventually leading to joint dysfunction and decreased quality of life [1,2]. Previous epidemiological surveys demonstrated that the global incidence of RA is 0.5-1% [1].…”