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Kjellqvist, Sanela
Publications (6 of 6) Show all publications
Gertow, J., Ng, C. Z., Branca, R. M., Werngren, O., Du, L., Kjellqvist, S., . . . Fisher, R. M. (2017). Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease. Kidney International Reports, 2(6), 1208-1218
Open this publication in new window or tab >>Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease
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2017 (English)In: Kidney International Reports, ISSN 2468-0249, Vol. 2, no 6, p. 1208-1218Article in journal (Refereed) Published
Abstract [en]

Introduction: Loss of renal function is associated with high mortality from cardiovascular disease (CVD). Patients with chronic kidney disease (CKD) have altered circulating adipokine and nonesterified fatty acid concentrations and insulin resistance, which are features of disturbed adipose tissue metabolism. Because dysfunctional adipose tissue contributes to the development of CVD, we hypothesize that adipose tissue dysfunctionality in patients with CKD could explain, at least in part, their high rates of CVD. Therefore we characterized adipose tissue from patients with CKD, in comparison to healthy controls, to search for signs of dysfunctionality. Methods: Biopsy samples of subcutaneous adipose tissue from 16 CKD patients and 11 healthy controls were analyzed for inflammation, fibrosis, and adipocyte size. Protein composition was assessed using 2dimensional gel proteomics combined with multivariate analysis. Results: Adipose tissue of CKD patients contained significantly more CD68-positive cells, but collagen content did not differ. Adipocyte size was significantly smaller in CKD patients. Proteomic analysis of adipose tissue revealed significant differences in the expression of certain proteins between the groups. Proteins whose expression differed the most were a-1-microglobulin/ bikunin precursor (AMBP, higher in CKD) and vimentin (lower in CKD). Vimentin is a lipid droplet-associated protein, and changes in its expression may impair fatty acid storage/mobilization in adipose tissue, whereas high levels of AMBP may reflect oxidative stress. Discussion: These findings demonstrate that adipose tissue of CKD patients shows signs of inflammation and disturbed functionality, thus potentially contributing to the unfavorable metabolic profile and increased risk of CVD in these patients.

Keywords
adipose tissue, alpha-1-microglobulin/bikunin precursor, cardiovascular disease, chronic kidney disease, proteomics, vimentin
National Category
Biological Sciences Other Clinical Medicine
Identifiers
urn:nbn:se:su:diva-152659 (URN)10.1016/j.ekir.2017.07.007 (DOI)000418639800023 ()29270529 (PubMedID)
Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2022-03-23Bibliographically approved
Kjellqvist, S., Klose, C., Surma, M. A., Hindy, G., Mollet, I. G., Johansson, A., . . . Fernandez, C. (2016). Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 5(12), Article ID e004503.
Open this publication in new window or tab >>Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction
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2016 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, E-ISSN 2047-9980, Vol. 5, no 12, article id e004503Article in journal (Refereed) Published
Abstract [en]

Background-Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. Methods and Results-We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmo Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18: 2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18: 2 (P <= 0.007) and lower desaturase activity (P <= 0.002). Conclusions-We demonstrate a possible relationship between decreased levels of C18: 2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases.

Keywords
diabetes mellitus, fatty acid desaturase, genotype, lipid metabolites, myocardial infarction
National Category
Biological Sciences Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:su:diva-139446 (URN)10.1161/JAHA.116.004503 (DOI)000390787700044 ()
Available from: 2017-02-23 Created: 2017-02-23 Last updated: 2024-07-04Bibliographically approved
Maleki, S., Kjellqvist, S., Paloschi, V., Magné, J., Branca, R. M., Du, L., . . . Björck, H. M. (2016). Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves. Scientific Reports, 6, Article ID 35712.
Open this publication in new window or tab >>Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves
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2016 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 35712Article in journal (Refereed) Published
Abstract [en]

Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:su:diva-136048 (URN)10.1038/srep35712 (DOI)000386004000001 ()27779199 (PubMedID)2-s2.0-84992671849 (Scopus ID)
Available from: 2017-01-03 Created: 2016-11-29 Last updated: 2022-09-15Bibliographically approved
Tuominen, R., Engstrom, P. G., Helgadottir, H., Eriksson, H., Unneberg, P., Kjellqvist, S., . . . Hoiom, V. (2016). The Role of Germline Alterations in the DNA Damage Response Genes BRIP1 and BRCA2 in Melanoma Susceptibility. Genes, Chromosomes and Cancer, 55(7), 601-611
Open this publication in new window or tab >>The Role of Germline Alterations in the DNA Damage Response Genes BRIP1 and BRCA2 in Melanoma Susceptibility
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2016 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 55, no 7, p. 601-611Article in journal (Refereed) Published
Abstract [en]

We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology. (C) 2016 Wiley Periodicals, Inc.

National Category
Bioinformatics and Systems Biology Medical Genetics
Identifiers
urn:nbn:se:su:diva-133239 (URN)10.1002/gcc.22363 (DOI)000379953500005 ()27074266 (PubMedID)
Available from: 2016-09-09 Created: 2016-09-05 Last updated: 2022-02-23Bibliographically approved
Bengtsson-Palme, J., Angelin, M., Huss, M., Kjellqvist, S., Kristiansson, E., Palmgren, H., . . . Johansson, A. (2015). The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents. Antimicrobial Agents and Chemotherapy, 59(10), 6551-6560
Open this publication in new window or tab >>The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents
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2015 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 10, p. 6551-6560Article in journal (Refereed) Published
Abstract [en]

Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

National Category
Microbiology Microbiology in the medical area
Identifiers
urn:nbn:se:su:diva-126412 (URN)10.1128/AAC.00933-15 (DOI)000367591800082 ()26259788 (PubMedID)
Available from: 2016-02-08 Created: 2016-02-01 Last updated: 2022-02-23Bibliographically approved
Lindholm, M. E., Huss, M., Solnestam, B. W., Kjellqvist, S., Lundeberg, J. & Sundberg, C. J. (2014). The human skeletal muscle transcriptome: sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing. The FASEB Journal, 28(10), 4571-4581
Open this publication in new window or tab >>The human skeletal muscle transcriptome: sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing
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2014 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, no 10, p. 4571-4581Article in journal (Refereed) Published
Abstract [en]

Human skeletal muscle health is important for quality of life and several chronic diseases, including type II diabetes, heart disease, and cancer. Skeletal muscle is a tissue widely used to study mechanisms behind different diseases and adaptive effects of controlled interventions. For such mechanistic studies, knowledge about the gene expression profiles in different states is essential. Since the baseline transcriptome has not been analyzed systematically, the purpose of this study was to provide a deep reference profile of female and male skeletal muscle. RNA sequencing data were analyzed from a large set of 45 resting human muscle biopsies. We provide extensive information on the skeletal muscle transcriptome, including 5 previously unannotated protein-coding transcripts. Global transcriptional tissue homogeneity was strikingly high, within both a specific muscle and the contralateral leg. We identified >23,000 known isoforms and found >5000 isoforms that differ between the sexes. The female and male transcriptome was enriched for genes associated with oxidative metabolism and protein catabolic processes, respectively. The data demonstrate remarkably high tissue homogeneity and provide a deep and extensive baseline reference for the human skeletal muscle transcriptome, with regard to alternative splicing, novel transcripts, and sex differences in functional ontology.

Keywords
gene expression profiling, biopsy, isoform, splice variant, novel transcript
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-108530 (URN)10.1096/fj.14-255000 (DOI)000342222700032 ()
Note

AuthorCount:6;

Available from: 2014-11-10 Created: 2014-10-29 Last updated: 2022-02-23Bibliographically approved
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