| 1. |
- Fernlund, Eva I., et al.
(author)
-
Serum biomarkers of early stages of hypertrophic cardiomyopathy in a young population
- 2015
-
In: Journal of the American College of Cardiology. - 0735-1097. ; 65:10S, s. 787-787
-
Conference paper (peer-reviewed)abstract
- Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder and the leading cause of sudden cardiac death in the young. Although in a majority of HCM cases there are gene mutations coding for sarcomere proteins, the onset for the clinical consequences of these mutations are difficult to predict, as these mutations do not show any clear relationship to the degree of myocardial hypertrophy. Hence identification of early markers for this disease is important. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis and coronary endotheliopathy in young presymtomatic HCM patients and in individuals at risk for developing HCM. Methods: Eighty-nine participants (18 HCM patients, 14 HCM-risk individuals, and 57 healthy controls) with median age of 15 (range 0-30) years underwent assessment with echocardiography and serum analysis for myostatin, cathepsin S, endostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP) 9, vascular (VCAM) and intercellular adhesion molecules (ICAM). In some individuals, myocardial perfusion was measured both at rest and after adenosine via magnetic resonance. Results: Both cathepsin S and endostatin were increased in the HCM group (p0.3) and diastolic function, expressed as E/e' (p0.3). In the HCM-risk group, myostatin was decreased (p0.1). Conclusion: To the best of our knowledge, this is the first study to suggest early onset changes in biomarkers of myoblast regulation, endothelial function and matrix remodeling in young presymptomatic HCM patients and in HCM-risk individuals.
|
|
| 2. |
- Glynn, A., et al.
(author)
-
Determinants of serum concentrations of perfluoroalkyl acids (PFAAs) in school children and the contribution of low-level PFAA-contaminated drinking water
- 2020
-
In: Environmental Science-Processes & Impacts. - : Royal Society of Chemistry (RSC). - 2050-7887 .- 2050-7895. ; 22:4, s. 930-944
-
Journal article (peer-reviewed)abstract
- Little is known about the demographic/life-style/physiological determinants explaining the variation of serum perfluoroalkyl acid (PFAA) concentrations in children. We identified significant determinants in children and investigated the influence of low-level PFAA-contaminated drinking water (DW) (<10 ng L(-1)of single PFAAs) on serum concentrations. Four perfluorosulfonic acids (PFSAs) and 11 perfluorocarboxylic acids (PFCAs) were analyzed in serum from 5(th)grade children from 11 Swedish schools (N= 200; average age: 12 years) using liquid chromatography-tandem-mass-spectrometry. Data on demography and life-style/physiological factors were obtained by questionnaires. PFAA concentrations in raw and drinking water (DW) were obtained from the water works supplying DW to the schools. In multiple regression analyses school was the determinant contributing most to the variation in PFAA concentrations, with the lowest contribution for PFHpA (10%) and the highest for PFHxS (81%). Girls had lower adjusted mean concentrations of PFHxS, PFOS, PFNA and PFDA than boys, but a higher concentration of PFHxA. Girls reporting onset of menstruation had lower PFHxS and PFOA concentrations than other girls, suggesting menstrual bleeding elimination. Children born by mothers from less industrialized countries had lower mean concentrations of both PFSAs and PFCAs than children with mothers from highly industrialized countries, suggesting differences in early-life exposure. Life-style factors associated with paternal education levels appeared to influence PFAA concentrations differently than maternal education level. Already at an average DW PFHxS concentration of 2 ng L-1, children had a significantly higher adjusted mean serum PFHxS concentration than at an average DW concentration of <1.6 ng PFHxS L-1. Similar results were observed for PFOS and PFOA. The DW variable explained 16% (PFOA) to 78% (PFHxS) of the variation in serum PFAA concentrations, suggesting that low-level-contaminated DW is a significant source of exposure for children in Sweden. Although some of the associations, especially those with menstruation and maternal birth country, should be interpreted with extra caution due to the small size of the study, the results contribute to future work on identifying populations of children at risk of elevated PFAA exposures.
|
|
| 3. |
|
|
| 4. |
- I. Fernlund, Eva, et al.
(author)
-
Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young
- 2017
-
In: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 38:4, s. 853-863
-
Journal article (peer-reviewed)abstract
- Hypertrophic cardiomyopathy (HCM) remains the leading cause of sudden cardiac death in the young. Early markers for HCM are important to identify individuals at risk. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis, and vascular endotheliopathy in the early stages of familial HCM in young patients. Twenty-three HCM patients, 16 HCM-risk individuals, and 66 controls (median 15 years) underwent echocardiography and serum analysis for cathepsin S, endostatin, myostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor receptor (VEGFR)-1, and vascular and intercellular adhesion molecules (VCAM, ICAM). In a subset of the population, global myocardial perfusion was performed by magnetic resonance imaging. Cathepsin S (p = 0.0009), endostatin (p < 0.0001), MMP-9 (p = 0.008), and VCAM (p = 0.04) were increased in the HCM group and correlated to left ventricular mass index and mitral E/e′ (p < 0.01). In the HCM-risk group, myostatin was decreased (p = 0.004), whereas ICAM was increased (p = 0.002). Global perfusion was decreased in the HCM group (p < 0.05) versus controls. Endostatin and mitral E/e′ correlated inversely to myocardial perfusion (p ≤ 0.05). This is the first study demonstrating adverse changes in biomarkers reflecting myocardial matrix remodeling, microfibrosis, and vascular endotheliopathy in early stage of hypertrophic cardiomyopathy in the young.
|
|
| 5. |
- Johanson, G., et al.
(author)
-
Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden
- 2023
-
In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 219
-
Journal article (peer-reviewed)abstract
- Contaminated drinking water (DW) is a major source of exposure to per- and polyfluoroalkyl substances (PFAS) at locations around PFAS production/use facilities and military airports. This study aimed to investigate quantitative relationships between concentrations in DW and serum of nine perfluoroalkyl acids (PFAAs) in Swedish adult populations living near contamination hotspots. Short-chained (PFPeA, PFHxA, PFHpA, and PFBS) and long-chained PFAAs (PFOA, PFNA, PFDA, PFHxS and PFOS) were measured in DW and serum. We matched DW and serum concentrations for a total of 398 subjects living or working in areas receiving contaminated DW and in one non-contaminated area. Thereafter, linear regression analysis with and without adjustments for co-variates was conducted. This enabled to derive (i) serum concentrations at background exposure (CB) from sources other than local DW exposure (i.e. food, dust and textiles) at 0 ng/L DW concentration, (ii) population-mean PFAA serum:water ratios (SWR) and (iii) PFAA concentrations in DW causing observable elevated serum PFAA concentrations above background variability. Median concentrations of the sum of nine PFAAs ranged between 2.8 and 1790 ng/L in DW and between 7.6 and 96.9 ng/mL in serum. DW concentration was the strongest predictor, resulting in similar unadjusted and adjusted regression coefficients. Mean CB ranged from <0.1 (PFPeA, PFHpA, PFBS) to 5.1 ng/mL (PFOS). Serum concentrations increased significantly with increasing DW concentrations for all PFAAs except for PFPeA with SWRs ranging from <10 (PFHxA, PFHpA and PFBS) to 111 (PFHxS). Observed elevated serum concentrations above background variability were reached at DW concentrations between 24 (PFOA) and 357 ng/L (PFHxA). The unadjusted linear regression predictions agreed well with serum concentrations previously reported in various populations exposed to low and high DW levels of PFOA, PFHxS and PFOS. The quantitative relationships derived herein should be helpful to translate PFAA concentrations in DW to concentrations in serum at the population level.
|
|
| 6. |
|
|
| 7. |
|
|
