| 1. |
- Grönholdt-Klein, Max, et al.
(författare)
-
Muscle atrophy and regeneration associated with behavioural loss and recovery of function after sciatic nerve crush
- 2019
-
Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 227:3
-
Tidskriftsartikel (refereegranskat)abstract
- Aim To resolve timing and coordination of denervation atrophy and the re-innervation recovery process to discern correlations indicative of common programs governing these processes. Methods Female Sprague-Dawley (SD) rats had a unilateral sciatic nerve crush. Based on longitudinal behavioural observations, the triceps surae muscle was analysed at different time points post-lesion. Results Crush results in a loss of muscle function and mass (-30%) followed by a recovery to almost pre-lesion status at 30 days post-crush (dpc). There was no loss of fibres nor any significant change in the number of nuclei per fibre but a shift in fibres expressing myosins I and II that reverted back to control levels at 30 dpc. A residual was the persistence of hybrid fibres. Early on a CHNR -epsilon to -gamma switch and a re-expression of embryonic MyHC showed as signs of denervation. Foxo1, Smad3, Fbxo32 and Trim63 transcripts were upregulated but not Myostatin, InhibinA and ActivinR2B. Combined this suggests that the mechanism instigating atrophy provides a selectivity of pathway(s) activated. The myogenic differentiation factors (MDFs: Myog, Myod1 and Myf6) were upregulated early on suggesting a role also in the initial atrophy. The regulation of these transcripts returned towards baseline at 30 dpc. The examined genes showed a strong baseline covariance in transcript levels which dissolved in the response to crush driven mainly by the MDFs. At 30 dpc the naive expression pattern was re-established. Conclusion Peripheral nerve crush offers an excellent model to assess and interfere with muscle adaptions to denervation and re-innervation.
|
|
| 2. |
- Lundback, Magnus, et al.
(författare)
-
Sex-specific risk of emergency department revisits and early readmission following myocardial infarction
- 2017
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 243, s. 54-58
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Readmissions within 30 days after hospitalization have been introduced as a measure of quality of care. There is a paucity of data regarding sex-specific risk of early readmissions after myocardial infarction (MI). Objectives: To investigate the association between sex and revisits to the emergency department (ED), and readmissions after MI. Methods: All patients with chest pain, diagnosed with MI at the Karolinska University Hospital during 2011 and 2012 were included. National Health care registers were used for information about patient characteristics, outcomes, and medication. We calculated risk ratios (RR) with 95% confidence intervals (CI) in women versus men, for revisits to the ED, readmission to hospital within 30, and 180 days, and to undergo coronary angiography, or revascularization, and to receive guideline-directed cardiovascular medication. Results: In total there were 667 patients with MI during the study period, of whom 197 (30%) were women. Womenwere older (mean age 73 vs. 65 years), and had more comorbidities thanmen. The 30-day risk of revisits to the ED was 1.56 times greater in women thanmen (adjusted RR 1.56 (1.09-2.25)). Throughout the first year; women were more likely to be readmitted than men, with the most striking difference found within 30 days (22% vs. 13%) of discharge (adjusted RR 1.54 (95% CI, 1.00-2.36)). There were no differences between men and women in new cardiovascular medication, coronary angiographies or revascularizations. Conclusions: Women have an increased risk of revisits to the ED, and readmissions to hospital during the first year after a MI.
|
|
| 3. |
- Rullman, Eric, et al.
(författare)
-
Mef2 as upstream regulator of the transcriptome signature in human skeletal muscle during unloading
- 2018
-
Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 315:4, s. R799-R809
-
Tidskriftsartikel (refereegranskat)abstract
- Our understanding of skeletal muscle structural and functional alterations during unloading has increased in recent decades, yet the molecular mechanisms underpinning these changes have only started to be unraveled. The purpose of the current investigation was to assess changes in skeletal muscle gene expression after 21 days of bed rest, with a particular focus on predicting upstream regulators of muscle disuse. Additionally, the association between differential microRNA expression and the transcriptome signature of bed rest were investigated. mRNAs from m. vastus lateralis biopsies obtained from 12 men before and after the bed rest were analyzed using a microarray. There were 54 significantly up-regulated probesets after bed rest, whereas 103 probesets were down-regulated (FDR 10%; fold-change cut-off ≥1.5). Amongst the up-regulated genes, transcripts related to denervation-induced alterations in skeletal muscle were identified, e.g. CHRND and perinatal myosin. The most down-regulated transcripts were functionally enriched for mitochondrial genes and genes involved in mitochondrial biogenesis, followed by a large number of contractile fiber components. Upstream regulator-analysis identified a robust inhibition of the MEF2 family, in particular MEF2C, which was suggested to act upstream of several key down-regulated genes, most notably PGC-1α/PPARs and CRSP3. Only a few microRNAs were identified as playing a role in the overall transcriptome picture induced by sustained bed rest. Our results suggest that the MEF2 family is a key regulator underlying the transcriptional signature of bed rest, and hence ultimately also skeletal muscle alterations induced by systemic unloading in humans.
|
|
| 4. |
- Sood, Sanjana, et al.
(författare)
-
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status
- 2015
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. Results: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. Conclusions: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.
|
|
| 5. |
- Steinz, Maarten M, et al.
(författare)
-
Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis
- 2019
-
Ingår i: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708 .- 2324-7703 .- 2325-4556. ; 4:9
-
Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here, we show that oxidative posttranslational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde (MDA) adduct modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located in 3 distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritic mice and patients with RA. Moreover, molecular dynamics simulations revealed that these areas, here coined "hotspots," are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and may provide novel leads for targeted therapeutic treatment to improve muscle function.
|
|
| 6. |
- Sundblad, Patrik, et al.
(författare)
-
Effects of training with flow restriction on the exercise pressor reflex
- 2018
-
Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 118:9, s. 1903-1909
-
Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that 5 weeks of endurance training with blood flow restriction (R-training), providing relative ischemia and stimulation of the muscle chemoreflex, would decrease the exercise pressor reflex (EPR) when compared to training with the same workload in a free-flow condition (NR-training). 10 subjects performed one-leg knee-extension training four times a week during a 5-week period. Both legs were trained with identical workload, with one leg being trained during flow-restriction induced by lower body positive pressure. The EPR was assessed by measuring the increase in heart rate (HR) and mean arterial pressure (MAP) during an isometric knee extension of 35% of max torque for 90 s, this was done before (C), and after training in each leg (R and NR, respectively). At the end of isometric contraction, the increase in mean AP (MAP) in the NR-trained leg and in the control condition were 41 +/- 4 and 38 +/- 4 mmHg, respectively, whereas the increase in the R-trained leg was 30 +/- 4 mmHg (p < 0.05 R vs C and NR), corresponding to a decrease of about 25%. A similar patter was observed with respect to responses in HR, where the increase was 28 +/- 3 and 28 +/- 3 bpm in the NR and C, and 22 +/- 4 in the R condition (p < 0.05 R vs C and NR). Peripheral metabolic changes induced by relative ischemia are important in modifying the EPR in response to exercise training.
|
|
