Roux-en-Y Gastric Bypass (RYGB) is a common treatment option for obesity. After RYGB, loss of both adipose tissue and lean body mass is seen. In this study, we have investigated the dynamic metabolic changes of hyaluronan (HA) and associated biomarkers reflecting the extracellular matrix after RYGB. In this exploratory cohort study, a total of 306 serum samples were collected at 5 different times from 96 RYGB patients, preoperatively until 6 months after surgery, where 44/96 (46

Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular hypertrophy. Mutations in genes for sarcomere proteins, e.g. in cardiac myosin-binding protein C (cMyBPC), cause symptoms like heart failure and sudden cardiac death. In HCM, the heart utilizes high amounts of glucose. Increased glucose metabolism creates intermediates for hyaluronan (HA) synthesis, resulting in HA accumulation within the extracellular space, which could contribute to cardiomyocyte hypertrophy. We aimed to describe the connection between HA and cardiomyocyte hypertrophy using cMyBPC+/- mice treated with two different β-blockers – either metoprolol or propranolol – for 11 months. The results showed that HA metabolism is altered in HCM, and consequently, HA is significantly more abundant in hearts of cMyBPC+/- mice compared to wild-type mice. High HA abundance correlated with increased cardiomyocyte size. Gene expression of HA synthase 2 was elevated in cMyBPC+/- mice. Treatment with propranolol significantly increased HA synthase 3 expression, while HA synthase 2 was maintained at wild-type level. Treatment with metoprolol or propranolol did not prevent HA accumulation nor decreased cardiomyocyte hypertrophy. These findings show a novel connection between high HA abundance and cardiomyocyte hypertrophy in cMyBPC+/- mice. ### Competing Interest Statement The authors have declared no competing interest. Norrländska Hjärtfonden, N/A Västerbotten County, RV-1035313, RV-1010683

Objectives There is a need for more specific biomarkers to diagnose and predict disease course in patients with axial spondyloarthritis (axSpA). This study aimed to study immunological plasma biomarkers, at different time-points in radiographic (r)-axSpA patients overall and stratified by sex and compare these biomarker pattern in r-axSpA patients concerning disease phenotypes and disease activity. Methods Plasma samples were analysed from r-axSpA patients at and prior (Pre-Backbone) inclusion in the Backbone study. Interferon gamma, interleukin-10, -17A, -17F, -22, -23, -6, MCP-1, TNF-α, VEGF-A, MIF, IgA anti-CD74, zonulin, ESR, hsCRP, white blood cell count, and blood lipids were measured. Results Biomarker pattern discriminated significantly between r-axSpA patients in Backbone and Pre-Backbone compared with controls. When stratifying by sex, it was possible to discriminate between male and female r-axSpA patients in Backbone vs controls and between male r-axSpA patients in pre-Backbone and controls. In Backbone, markers with high discriminative capacity were MIF, IgA anti-CD74, and MCP-1. In Pre-Backbone, IL-6, TNF-α, MIF, triglycerides, cholesterol, IL-10, and zonulin displayed high discriminative capacity. Conclusion Based on their temporal pattern and mutual relationship, we suggest studying MIF, IgA anti-CD74, and MCP-1 in depth, at more time points, to further elucidate disease-driving mechanisms in this complex disease.

ABSTRACT We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1–5) and severe COVID-19 (WHO-CPS, 6–9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment. IMPORTANCE This study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies.

Objective There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA. Method In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations. Results Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean ± SD, 0.8 ± 0.1 mm vs 0.7± 0.1 mm, respectively, unstandardized β (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean ± SD, 6.8 ± 1.6 10 9 /L) and monocytes (0.6 ± 0.2 10 9 /L); WBC count (unstandardized β (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R 2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R 2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP. Conclusion Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis. Key Points • Carotid intima-media thickness was increased in patients with radiographic axial spondyloarthritis compared to controls. • White blood cell and monocyte counts were associated with carotid intima-media thickness in male patients with radiographic axial spondyloarthritis.

Abdominal hernia is a protruding weakness in the abdominal wall. It affects abdominal strength and life quality and can lead to complications due to intestinal entrapment. Autologous full-thickness skin graft (FTSG) has recently become an alternative material for reinforcement in the surgical repair of large abdominal hernias instead of synthetic mesh. FTSG eventually integrates with the abdominal wall, but the long-term fate of the graft itself is not fully understood. This has implications as to how these grafts should be optimally used and handled intraoperatively. This study investigates the remodeling of FTSG in either the onlay or the intraperitoneal position 8 weeks after FTSG transplantation in an experimental mouse model. There was a significant presence of fibroblasts, indicated by vimentin and S100A4 staining, but there were significant variations among animals as to how much of the graft had been remodeled into dense connective tissue. This correlated significantly with the proportion of vimentin-positive cells in the dense connective tissue. We also found that collagen hybridizing peptide staining intensity, a marker of active remodeling, was significantly associated with the proportion of S100A4-positive cells in the dense connective tissue of the FTSG.

Abstract Background Epicardial adipose tissue (EAT) has direct contact with the myocardium, which enables a common microcirculation allowing bidirectional signaling between the tissues. It is possible that a change in the balance of protective and damaging mediators produced by EAT is a major driver for myocardial dysfunction. Notably, EAT volume and thickness associate with increased pro-inflammatory secretome and with coronary artery disease (CAD). Purpose This aim of this study was to analyze the total transcriptome in EAT and relate putative differences between patient groups to metabolic parameters as well as ongoing medications. Methods Between 2011 and 2016, 44 patients (mean age 68.0 years, 18.2% women) had a biopsy taken from the epicardial fat during coronoray by-pass surgery (CABG, n=36), or during elective aortic valvular replacement due to aortic stenosis (AVR, n=8). RNA from epicardial fat biopsis was extracted and sequenced. Differentially expressed genes were obtained by custom scripts that performed a negative binomial distribution test on effective counts. Multivariate regression analysis with orthogonal partial least-squares-discriminant analysis (OPLS-DA) was applied to extract and interpret the systematic variation in the resolved RNA sequencing profiles. To identify enrichment of biologically relevant functional gene sets, our data were entered in evidence-based network enrichment analysis (EviNet). Results The CABG surgery was performed approximately 7 days after an acute coronary event (75% acute MI), and 44% of them had previously known CAD. None of the AVR cases had significant CAD. At surgery, 97% of the CABG cases were prescribed statins, and 36% of them had statins alredy before the actual admission (long-term statin treatment). 63% of the AVR cases were on statins at admission. The OPLS analysis revealed only one medication with significant outcome, i.e., patients with long-term treatment with statins (n=18) versus patients without (n=26). Long-term statin treatment associated with down-regulated gene expression involved in beta-oxidation and triglyceride biosynthesis whereas gene expression involved in extracellular matrix organization were up-regulated. Gene expression involved in MHC class II presentation and interferon signalling were also reduced in patients with long-term treatment with statisn. A downregulation of genes in the interleukin- and complement cascade genes among CABG patient (versus AVR patients) without long-term statin treatment showed normal levels in statin pretreated patients. Conclusion Long-term statin treatment has a major influence on transcriptional regulation of genes involved in beta-oxidation, triglyceride biosynthesis, extracellular matrix composition, MHC class II presentation and interferon signalling in epicardial adipose tissue. These findings support important metabolic and immune effects of statins beyond the lipid-lowering function.

ABSTRACT Background We have previously shown that lungs from deceased COVID-19 patients are filled with hyaluronan (HA). In this translational study, we investigated the role of HA in all stages of COVID-19 disease, to map the consequences of elevated HA in morbidity and identify the mechanism of SARS-CoV-2-induced HA production. Methods Lung morphology was visualized in 3D using light-sheet fluorescence microscopy. HA was verified by immunohistochemistry, and fragmentation was determined by gas-phase electrophoretic molecular mobility analysis. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS 6-9), during the acute and convalescent phases and related to lung function. In vitro 3D-lung models differentiated from primary human bronchial epithelial cells were used to study effects of SARS-CoV-2 infection on HA metabolism. Findings Lungs of deceased COVID-19 patients displayed reduced alveolar surface area compared to healthy controls. We verified HA in alveoli and showed high levels of fragmented HA both in lung tissue and aspirates. Systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence and associated with reduced diffusion capacity. Transcriptomic analysis of SARS-CoV-2-infected lung models showed dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Corticosteroid treatment reduced inflammation and, also, downregulated HA synthases. Interpretation We show that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment. SARS-CoV-2 infection triggers a dysregulation of HA production, leading to increased concentrations of HA that are partially counteracted by corticosteroid treatment. Treatments directly targeting HA production and/or degradation can likely be used early during infection and may alleviate disease progression and prevent long-term lung complications.

The purpose of this study was to study CD4+CXCR5+ T follicular helper (TFH) cells, CD27+CD38+ plasmablasts and CD27+CD38- memory B cells, as well as disease-related factors in patients with ankylosing spondylitis (AS) from northern Sweden. Peripheral blood mononuclear cells (PBMC) from 50 patients with AS (mean age 52 +/- 9 years, 66% men, 100% HLA-B27 positive) and 50 pairwise matched blood donor controls (mean age 54 +/- 9 years, 66% men) were stained with antibodies for CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analysed by flow cytometry. Patients with AS were examined with spinal x-ray for radiographic alterations (mSASSS), and plasma levels of C-reactive protein, erythrocyte sedimentation rate, as well as selected proinflammatory and regulatory cytokines were determined. Physical mobility, function and disease activity were registered by BASMI, BASFI and ASDAS-CRP, BASDAI, respectively. Comparing AS patients and controls pairwise, we observed a 56% reduction of TFH cells in PBMCs from AS patients (P = .000008). Furthermore, a 20%-30% reduction in plasmablasts and B memory cells (P <= .002 and P <= .007, respectively) was observed. In female patients, negative correlations between ESR and TFH, plasmablasts and B memory cells were observed; Rs = -0.551, P <= .02; Rs = -0.476, P <= .05 and Rs = -0.522, P <= .03, respectively. In addition, positive correlations between the regulatory cytokine IL-10 and the proportion of B cells, IL-22, and the proportion of plasmablasts as well as a negative correlation between levels of the proinflammatory cytokine IL-6 and TFH were detected. Our observations indicate a role of an aberrant humoral immune response related to inflammation in AS.

Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort. The 30,154 study participants, 50–64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination. Study participants with prediabetes (n = 4804, 16.0

A solid phase adsorption method for selective isolation of hyaluronan (HA) from biological samples is presented. Following enzymatic degradation of protein, HA can be separated from sulfated glycosaminoglycans, other unsulfated glycosaminoglycans, nucleic acids, and proteolytic fragments by adsorption to amorphous silica at specific salt concentrations. The adsorbed HA can be released from silica using neutral and basic aqueous solutions. HA ranging in size from ∼9 kDa to MDa polymers has been purified by this method from human serum and conditioned medium of cultured cells.

Ankylosing spondylitis (AS) is an autoimmune disease affecting parts of the skeletal structure in particular. Previously increased levels of the inflammatory cell types Th17, Th22, Tc17 and Tc22 cells have been shown to be associated with AS. Here, we analysed the levels of inflammatory T cell subsets, related cytokines and clinical characteristics of AS patients vs controls from northern Sweden. Peripheral blood mononuclear cells (PBMCs) obtained from 50 AS patients and 50 matched controls were short term stimulated with PMA/Ionomycin, stained and analysed by flow cytometry. Plasma levels of Interleukin (IL)-17, IL-22, IL-10 as well as clinically relevant markers were determined. Compared to male controls, male AS patients showed 1.5- to 2-fold increases of Th17 (P = .013), Th22 (P = .003) and Tc22 (P = .024) among CD45+ CD3+ lymphocytes. Plasma IL-22 levels correlated with the Tc17 proportion in male patients (Rs = 0.499, P = .003) and plasma IL-10 levels were inversely correlated with Tc17 among all patients (Rs = -0.276, P = .05). Male patients with syndesmophytes showed significantly higher Th17 proportions (P = .038). In female AS patients, Tc22 was negatively correlated with C-reactive protein (high sensitivity) (hsCRP) (Rs = -0.573, P = .016). We confirmed increased proportions of inflammatory T cells and correlations with relevant cytokines from male AS patients. The correlation between Th17 and syndesmophytes supports a role of Th17 in the pathogenic process.

Background Increased levels of TH17 and TH22 as well as TC17 and TC22 cells and their related cytokines have previously been associated with ankylosing spondylitis (AS). However, the status of these inflammatory cells in a well characterized AS cohort from northern Sweden has not been studied. Objectives The aim of this study was to confirm the increased presence of inflammatory T cell subsets in peripheral blood of patients with AS and controls from northern Sweden and explore the association with clinically relevant parameters with the level of the inflammatory T cell subset(s) and related cytokines. Methods Peripheral blood mononuclear cells (PBMCs) from a cohort of 50 patients (66% men) with AS from Region Västerbotten (age 52.1±9.0 years, 100% HLA-B27+) and 50 pairwise sex- and age-matched blood donor controls (66% men, mean age 54.6±9.1 years) were stained for CD45, CD3, CD4, CD8, intracellular IL-17 and IL-22 and analyzed by flow cytometry. In addition, levels of IL-17, IL-22 and IL-10 in plasma were determined. The patients with AS were assessed for mSASSS, hsCRP, ESR, BASMI, BASFI, ASDAS-hsCRP and BASDAI. Results Pairwise comparisons of AS patients and controls showed a 1,5x to 2-fold increase of TH17, TH22 and TC22 cells among CD45+CD3+ lymphocytes in PBMCs in male patients ( p =0.013, p =0.003 and p =0.024 respectively). Levels of IL-22 in plasma and proportion of TC17 correlated in male patients (R s =0.499 p =0.003) and plasma levels of IL-10 showed an inverse correlation to TC17 in all patients (R s =-0.276 p =0.05). In addition, male patients with ≥ 1 syndesmophyte showed significantly higher proportion of TH17 cells ( p =0.038). In female AS patients there was a negative correlation between TC22 and hsCRP (R s = -0.573, p=0.016). Conclusions We confirm an increased proportion of TH17, TH22 and TC22 cells in blood in AS male patients from northern Sweden. A positive correlation with the proinflammatory cytokine IL-22 and reverse correlation of the anti-inflammatory cytokine IL-10 in relation to TC17 corroborate the influence of these cells. In addition, a role of TH17 in the pathogenesis process is supported by the correlation between TH17 proportions and the presence of ≥ 1 syndesmophyte.

Untargeted metabolomics is a well-established technique and a powerful tool to find potential plasma biomarkers for early diagnosing hereditary transthyretin amyloidosis. Hereditary transthyretin amyloidosis (ATTRv) is a disabling and fatal disease with different clinical features such as polyneuropathy, cardiomyopathy, different gastrointestinal symptoms and renal failure. Plasma specimens collected from 27 patients with ATTRv (ATTRV30M), 26 asymptomatic TTRV30M carriers and 26 control individuals were subjected to gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS)-based metabolomics analysis. Partial least squares discriminant and univariate analysis was used to analyse the data. The models constructed by Partial least squares-discriminant analysis (PLS-DA) could clearly discriminate ATTRV30M patients from controls and asymptomatic TTRV30M carriers. In total, 24 plasma metabolites (VIP > 1.0 and p < .05) were significantly altered in ATTRV30M patient group (6 increased and 18 decreased). Eleven of these distinguished the ATTRV30M group from both controls and TTRV30M carriers. Plasma metabolomics analysis revealed marked changes in several pathways in patients with ATTRV30M amyloidosis. Statistical analysis identified a panel of biomarkers that could effectively separate controls/TTRV30M carriers from ATTRV30M patients. These biomarkers can potentially be used to diagnose patients at an early stage of the disease.

Objectives Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes. Methods IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI and BASMI were assessed and spinal radiographs were scored for r-axSpA-related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden. Results A total of 155 patients comprising 69% men and 31% women, age [mean (s.d.)] 55.5 (11.4)years and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients [median (interquartile range), 12.9 (7.9-17.9) U/ml] compared with controls [10.9 (7.2-14.6) U/ml, P=0.003]. IgA anti-CD74 was above the cut-off level of 20U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls (P=0.002). Multivariable logistic regression analyses revealed >= 1 syndesmophyte associated with IgA anti-CD74 (odds ratio 5.64; 95% CI: 1.02, 35.58; P=0.048) adjusted for hsCRP, smoking, BMI, sex and age. No distinct pattern of IgA anti-CD74 over time was revealed. Conclusion Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes, which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.

Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference.  In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.

Severe coronavirus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined. The aim of the study was to demonstrate whether the lungs of fatal Covid-19 contain hyaluronan, as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly. Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue. Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.

Background/Purpose: Increased levels of TH17 and TH22 as well as TC17 and TC22 cells have previously been associated with ankylosing spondylitis (AS). The correlation between these inflammatory T c ...

During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.

Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab. Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients’ assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined. Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution. Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.