Antibodies to malondialdehyde-acetaldehyde modified low-density lipoprotein in patients with newly diagnosed inflammatory joint disease.

Objective:To assess antibodies to malondialdehyde-acetaldehyde-modified low-density lipoprotein (MAA-LDL) in patients with newly diagnosed inflammatory joint disease.Method: Patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA), participating in the Northern Savo 2010 Study, were evaluated for metabolic syndrome (MetS), metabolic and inflammatory markers, antibodies to MAA-LDL, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis.Results: Among 135 newly diagnosed untreated patients, of whom 53 (39%) were diagnosed to have RA, 44 (33%) SpA, and 38 (28%) UA, 49%, 30%, and 47%, respectively, had MetS. After adjusting for age and gender, anti-MAA-LDL immunoglobulin (Ig)A (p = 0.009), IgG (p = 0.031), and IgM (p = 0.001) levels differed between the diagnostic categories, but not in patients with MetS present or absent. All antibody classes to MAA-LDL correlated with erythrocyte sedimentation rate (ESR), and IgA and IgG antibodies with high-sensitivity C-reactive protein (hs-CRP). IgA antibodies to MAA-LDL correlated with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), fasting plasma glucose, IgA antibodies to A. actinomycetemcomitans, and in IgA and IgG antibodies to P. gingivalis.Conclusion: Among various arthritis groups, antibodies to MAA-LDL were most common in RA. Antibodies to modified lipoproteins were associated with inflammation measured by ESR and hs-CRP. IgA antibodies to MAA-LDL correlated with age, antibodies to periodontal bacteria, RF, ACPA, and fasting glucose. Associations between antibodies to MAA-LDL and antibodies to periodontal bacteria, RA-associated antibodies, inflammatory parameters, and plasma glucose already reflect cardiovascular burden in inflammatory joint diseases at diagnosis.

Incidence of inflammatory joint diseases in Finland: results from a population-based epidemiological study.

The objective of the study was to assess the incidence of inflammatory joint diseases and possible environmental factors contributing to their occurrence in a defined population in Finland. All rheumatologists practising in the Northern Savo rheumatological outpatient departments collected data on their newly diagnosed patients with an inflammatory joint disease in 2010. Antibodies to Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) were determined from patients with various arthritides. The incidence of all arthritis cases was 141.8/100,000 (95% CI 126.1-159.1). Eighty-six patients, 43 men and 43 women, satisfied the ACR/Eular 2010 classification criteria for rheumatoid arthritis (RA) yielding an annual incidence of 41.6/100,000 (33.3-51.4), 42.5 (30.8-57.3) for men and 40.8 (29.9-56.1) for women. The incidence of chronic spondyloarthritides was 36.3 (28.6-45.5), reactive arthritis 7.8 (4.4-12.6), undifferentiated arthritis 38.7 (30.7-48.2), and crystalline arthritis 15.0 (10.2-21.3). Immunoglobulin A (IgA) antibody levels to Pg were higher among men, patients with anti-cyclic citrullinated peptide antibodies (ACPA) or missing teeth and AaIgA antibody levels in patients with missing teeth. In RA, 67 % of men and 35% of women had a smoking history, p = 0.012. There was no difference between the genders in the incidence of RA, which might be explained by a higher carriage of periodontal bacteria and a higher smoking rate among men. In other disease categories, the incidences were comparable to those earlier reported. By influencing behavioral and environmental factors, it might be possible to reduce the burden of ACPA-positive RA.

Estimating the incidence of connective tissue diseases and vasculitides in a defined population in Northern Savo area in 2010.

Objective of the study was to evaluate the annual incidence and distribution of autoimmune connective tissue diseases and vasculitides during 2010. All units practicing rheumatology in the Northern Savo area, Finland, participated in the study by collecting data on newly diagnosed adult patients with autoimmune connective tissue disease or vasculitis over 1-year period. Seventy-two cases with autoimmune connective tissue disease were identified. The annual incidence rates were as follows: systemic lupus erythematosus 3.4/100,000 (95 % CI 1.4-7.0), idiopathic inflammatory myopathies 1.9 (0.5-5.0), systemic sclerosis 4.4 (2.0-8.3), mixed connective tissue disease 1.0 (0.1-3.5), Sjögren's syndrome 10.7 (6.7-16.1) and undifferentiated connective tissue disease 13.6 (9.0-19.6). The annual incidence rates among vasculitis category were as follows: antineutrophil cytoplasmic antibody-associated vasculitis 1.5/100,000 (95 % CI 0.3-4.3), central nervous system vasculitis 0.5 (0-2.7) and Henoch-Schönlein purpura 1.5 (0.3-4.3). The annual incidence of giant cell arteritis in the age group of 50 years or older was 7.5/100,000 (95 % CI 3.2-14.8). The longest delay from symptom onset to diagnosis occurred in systemic sclerosis. The incidences of autoimmune connective tissue diseases and vasculitides were comparable with those in published literature. The present study showed female predominance in all connective tissue diseases, excluding idiopathic inflammatory muscle diseases and mean age at onset of disease around 50 years of age. Despite improved diagnostic tools, diagnostic delay is long especially among patients with systemic sclerosis.

PDGF-C and -D and their receptors PDGFR-alpha and PDGFR-beta in atherosclerotic human arteries.

BACKGROUND: Platelet derived growth factors (PDGFs) are mitogens for fibroblasts and smooth muscle cells. This growth factor family contains four members PDGF-A, PDGF-B, PDGF-C and PDGF-D. Biology of recently discovered PDGF-C and PDGF-D is not well-established. Here we studied the expression of PDGF-C and PDGF-D and their receptors PDGFR-alpha and PDGFR-beta in normal and atherosclerotic human arteries. MATERIALS AND METHODS: Human arterial samples from amputations and autopsies were classified according to the atherosclerotic stage and the expression of PDGF-C and PDGF-D proteins and their receptors was studied by immunohistochemistry. In situ hybridization and reverse transcriptase-PCR were used to study mRNA expression. RESULTS: Both growth factors were expressed in medial smooth muscle cells (SMCs) in normal arteries and atherosclerotic lesions. However, clear differences were found in the expression profiles in endothelium: PDGF-C was strongly expressed in endothelial cells in both normal arteries and lesions whereas PDGF-D was only weakly expressed in endothelium. PDGF-C expression was very prominent in lesion macrophages. PDGF-D was expressed throughout the artery wall in lesions. PDGFR-alpha expression was strong in endothelium and in lesion macrophage-rich areas, whereas PDGFR-beta was mostly expressed in SMCs. CONCLUSIONS: Our results suggest that PDGF-C may play an important role in endothelium in normal and atherosclerotic arteries and in macrophages in lesions. PDGF-D was expressed in all types of lesions with the same intensity and thus differs from the expression of PDGF-C.

Gene transfer using the mature form of VEGF-D reduces neointimal thickening through nitric oxide-dependent mechanism.

Gene transfer to the vessel wall using vascular endothelial growth factors (VEGFs) has shown therapeutic potential for the treatment of restenosis. In this study, we evaluated the effect of catheter-mediated adenoviral (Ad) gene transfer of the mature form of VEGF-D (VEGF-D(DeltaNDeltaC)) in balloon-denuded cholesterol-fed rabbit aorta. AdLacZ was used as a control. Transduced VEGF-D(DeltaNDeltaC) mRNA was detectable in the arterial wall with RT-PCR at 6, 14 and 28 days. Gene transfer efficiency as detected with X-gal staining 6 days after the AdLacZ transduction was 1.91 +/- 1.32% in intima. AdVEGF-D(DeltaNDeltaC) gene transfer led to 52% reduction in intima/media ratio (I/M) as compared to the AdLacZ controls at 14 days time point. At 6 days there were no differences in I/M, but the number of macrophages in the vessel wall was 85% lower in the AdVEGF-D(DeltaNDeltaC) group as compared to the controls. The therapeutic effect was no longer detectable 28 days after the gene transfer. The therapeutic effect of VEGF-D(DeltaNDeltaC) was nitric oxide (NO)-dependent as the feeding of NO synthase inhibitor, L-NAME, blocked the reduction in intimal thickening. It is concluded that AdVEGF-D(DeltaNDeltaC) gene transfer reduces intimal thickening and macrophage influx into the vessel wall in balloon-denuded rabbit aortas.

Post-intervention vessel remodeling.

By-pass surgery and percutaneous transluminal (coronary) angioplasty, PT(C)A, are standard techniques for the treatment of vascular occlusions. Their usefulness is limited by by-pass graft failure and restenosis occurring after the procedures. Twenty percent of patients treated with PTCA/PTA need a new revascularization procedure within 6 months, despite a successful procedure. Stents are used to prevent restenosis in selected lesions, but in-stent restenosis also remains an important clinical problem. In this review we discuss progress of gene therapy for the treatment of post-PT(C)A restenosis, in-stent restenosis and by-pass graft stenosis over the last 2 years (2000-2002).

Clinical applications of vascular gene therapy.

Despite significant advances in prevention, coronary artery disease remains the leading cause of death in the Western world. Surgical bypass and angioplasty are the primary interventional therapies but they are limited by the problems of restenosis and graft occlusions. Natural response to vascular occlusion involves the formation of collateral vessels that bypass obstructions, but they are often inefficient in relieving ischemia. Vascular gene transfer offers a promising new approach to solve these problems. Its potential has been shown in animal models and in first human trials using vascular endothelial growth factor, fibroblast growth factor, and E2F cell-cycle transcription factor decoy. However, further basic research on gene transfer vectors, gene delivery techniques, and identification of effective treatment genes is needed to improve the efficacy and safety of human vascular gene therapy.