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- Becirovic-Agic, Mediha, et al.
(författare)
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Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome
- 2019
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : the American Physiological Society. - 0363-6119 .- 1522-1490. ; 316:5, s. R563-R570
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.
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- Jönsson, Sofia, et al.
(författare)
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Angiotensin II and salt-induced decompensation in Balb/CJ mice is aggravated by fluid retention related to low oxidative stress
- 2019
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:5, s. F914-F933
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Tidskriftsartikel (refereegranskat)abstract
- Balb/CJ mice are more sensitive to treatment with angiotensin II (ANG II) and high-salt diet compared with C57BL/6J mice. Together with higher mortality, they develop edema, signs of heart failure, and acute kidney injury. The aim of the present study was to identify differences in renal gene regulation that may affect kidney function and fluid balance, which could contribute to decompensation in Balb/CJ mice after ANG II + salt treatment. Male Balb/CJ and C57BL/6J mice were divided into the following five different treatment groups: control, ANG II, salt, ANG II + salt. and ANG II + salt + N-acetylcysteine. Gene expression microarrays were used to explore differential gene expression after treatment and between the strains. Published data from the Mouse Genome Database were used to identify the associated genomic differences. The glomerular filtration rate (GFR) was measured using inulin clearance, and fluid balance was measured using metabolic cages. Gene ontology enrichment analysis of gene expression microarrays identified glutathione transferase (antioxidant system) as highly enriched among differentially expressed genes. Balb/CJ mice had similar GFR compared with C57BL/6J mice but excreted less Na+ and water, although net fluid and electrolyte balance did not differ, suggesting that Balb/CJ mice may be inherently more prone to decompensation. Interestingly, C57BL/6J mice had higher urinary oxidative stress despite their relative protection from decompensation. In addition, treatment with the antioxidant N-acetylcysteine decreased oxidative stress in C57BL/6J mice, reduced urine excretion, and increased mortality. Balb/CJ mice are more sensitive than C57BL/6J to ANG II + salt, in part mediated by lower oxidative stress, which favors fluid and Na+ retention.
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- Vilà C., Leonard J.A., Götherstöm A., Marklund S., Sandberg K., Lidén K., Wayne R.K., Ellegren H.
(författare)
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Widespread origins of domestic horse lineages
- 2001
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Ingår i: Science. ; 291, s. 474-477
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Tidskriftsartikel (refereegranskat)
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- Wahlberg, K., et al.
(författare)
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Filaggrin variations are associated with PAH metabolites in urine and DNA alterations in blood
- 2019
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment. © 2019
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- Agvall, B., et al.
(författare)
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Characteristics, management and outcomes in patients with CKD in a healthcare region in Sweden: a population-based, observational study
- 2023
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Ingår i: Bmj Open. - London : BMJ Publishing Group Ltd. - 2044-6055. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo describe chronic kidney disease (CKD) regarding treatment rates, comorbidities, usage of CKD International Classification of Diseases (ICD) diagnosis, mortality, hospitalisation, evaluate healthcare utilisation and screening for CKD in relation to new nationwide CKD guidelines. DesignPopulation-based observational study. SettingHealthcare registry data of patients in Southwest Sweden. ParticipantsA total cohort of 65 959 individuals aged >18 years of which 20 488 met the criteria for CKD (cohort 1) and 45 470 at risk of CKD (cohort 2). Primary and secondary outcome measuresData were analysed with regards to prevalence, screening rates of blood pressure, glucose, estimated glomerular filtration rate (eGFR), Urinary-albumin-creatinine ratio (UACR) and usage of ICD-codes for CKD. Mortality and hospitalisation were analysed with logistic regression models. ResultsOf the CKD cohort, 18% had CKD ICD-diagnosis and were followed annually for blood pressure (79%), glucose testing (76%), eGFR (65%), UACR (24%). UACR follow-up was two times as common in hypertensive and cardiovascular versus diabetes patients with CKD with a similar pattern in those at risk of CKD. Statin and renin-angiotensin-aldosterone inhibitor appeared in 34% and 43%, respectively. Mortality OR at CKD stage 5 was 1.23 (CI 0.68 to 0.87), diabetes 1.20 (CI 1.04 to 1.38), hypertension 1.63 (CI 1.42 to 1.88), atherosclerotic cardiovascular disease (ASCVD) 1.84 (CI 1.62 to 2.09) associated with highest mortality risk. Hospitalisation OR in CKD stage 5 was 1.96 (CI 1.40 to 2.76), diabetes 1.15 (CI 1.06 to 1.25), hypertension 1.23 (CI 1.13 to 1.33) and ASCVD 1.52 (CI 1.41 to 1.64). ConclusionsThe gap between patients with CKD by definition versus those diagnosed as such was large. Compared with recommendations patients with CKD have suboptimal follow-up and treatment with renin-angiotensin-aldosterone system inhibitor and statins. Hypertension, diabetes and ASCVD were associated with increased mortality and hospitalisation. Improved screening and diagnosis of CKD, identification and management of risk factors and kidney protective treatment could affect clinical and economic outcomes.
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