Biology subjects

Wiens, L.

Publications and source records attributed to Wiens, L..

3 recordsLinked to original sources

bioRxiv2026

Leg blood flow and muscle oxygenation are reduced when exercising with loads >=40% 1RM compared to loads <=30% 1RM due to increases in contraction induced intramuscular pressure

The critical occluding tension (COT) is the load at which contraction-induced increases in intramuscular pressure (IMP) collapse intramuscular vasculature and impair oxygen delivery. For knee extension resistance exercise, the COT occurs at ~30-40% 1RM, yet few studies have measured IMP alongside convective oxygen delivery. This study examined the interaction between IMP, leg blood flow, and muscle oxygenation during resistance exercise. Twelve participants completed knee extension bouts across a range of loads while vastus lateralis IMP, femoral blood flow (Doppler), blood pressure, muscle oxygenation (NIRS), and electromyography (EMG) were recorded. Mean IMP increased alongside relative load (20% 1RM=19.1(9.4) mmHg; 30% 1RM=22.4(10.4) mmHg; 40% 1RM=27.0(8.7) mmHg; 50% 1RM=31.5(11.5) mmHg; 60% 1RM=41.14(13.8) mmHg; p<0.05). Leg blood flow scaled to rest was similar between 20% and 30% 1RM (p=0.13), 40%, 50%, and 60% 1RM (p>0.05), but different between the 20-30% 1RM and 40-60% 1RM groupings (p<0.05) (20% 1RM=2.6(1.4) times rest; 30% 1RM=1.8(0.5) fold of rest; 40% 1RM=1.4(0.6) fold of rest; 50% 1RM=1.1(0.4) fold of rest; 60% 1RM=1.1(0.5) fold of rest). Muscle oxygenation was lower at 40%, 50%, and 60% 1RM compared to 20% and 30% 1RM (p<0.05). Thus, at [≤]30% 1RM exercising blood flow increased well above rest, indicating preserved microvascular perfusion, whereas at [≥]40% 1RM the rise in IMP was sufficient to impair perfusion and limit blood flow increases. Exercise at or above the COT restricts convective oxygen delivery due to contraction-induced increases in IMP.

physiology↗

bioRxiv2026

Matrix Metalloproteinase Response to Acute Resistance Exercise is Altered in Osteoarthritic Adults with Increased Muscle Collagen and PDGFRα+ Mesenchymal Cells

Background: Knee osteoarthritis (OA) is associated with knee extensor weakness, altered myofibre morphology, reduced satellite cell abundance and fibrillar muscle collagen accumulation in the vastus lateralis (VL). Fibrillar muscle collagen accumulation is associated with reduced knee extensor strength. Yet, its underlying mechanisms remain poorly understood. Satellite cells and PDGFR+ mesenchymal cells express collagen as well as proteins involved in collagen degradation and may be involved in muscle collagen accumulation. The present study assessed knee extensor function and myofibre morphology, satellite cells and PDGFR+ mesenchymal cells in adults with and without moderate-to-severe knee OA. It also investigated collagen remodeling by assessing how enzymes involved in collagen degradation (matrix metalloproteinases [MMPs]) respond to acute resistance exercise in the VL. This study aimed to better understand the cellular contributors to muscle collagen accumulation and knee extensor weakness in knee OA. Methods: Volunteers with and without moderate-to-severe knee OA had a resting muscle biopsy, then completed an acute bout of resistance exercise and had a 72-hour post-exercise biopsy. Knee extensor strength was measured on a Biodex dynamometer. In VL samples, MMP gene expression (qPCR), protein area fraction (immunofluorescence) and enzyme activity (zymography) were assessed. PDGFR+ mesenchymal cells, satellite cells, satellite cell-MMP9 colocalization and myofibre morphology were assessed by immunofluorescence. Fibrillar muscle collagen content was quantified by picrosirius red. Results: Participants with moderate-to-severe knee OA had weaker knee extensors (isometric and isokinetic), reduced muscle quality (isometric and isokinetic) and more fibrillar collagen than controls (12.2 {+/-} 4.8%, 8.4 {+/-} 2.9%, p = 0.006). Fibrillar collagen was negatively correlated with isokinetic concentric torque (r = -0.479, p = 0.006). Volunteers with knee OA had more PDGFR+ mesenchymal cells (p < 0.001) and fewer satellite cells than controls (p = 0.006). In both groups, resistance exercise upregulated MMP2 (p < 0.001), MMP9 (p = 0.001) and MMP14 (p < 0.001) gene expression as well as MMP2 (p < 0.001) and MMP9 (p = 0.001) enzyme activity. MMP2 and MMP9 protein area fraction increased in response to resistance exercise in controls, but this response was blunted in the knee OA group (age x time interaction, p = 0.041). Satellite cell-MMP9 colocalization fold change post-exercise was significantly different between groups (p = 0.048). Volunteers with knee OA had smaller myofibres (p < 0.001) and greater myofibre shape irregularity (p = 0.039), but no differences in thigh lean mass, capillary content or fibre-type distribution. Conclusions: Although exercise stimulated transcriptional and MMP activity responses in both groups, the ECM-specific protein response was impaired in knee OA. The findings suggest that dysregulated ECM remodeling facilitated by MMPs and alterations in PDGFR+ mesenchymal and satellite cell abundance may contribute to muscle collagen accumulation and knee extensor weakness in knee OA.

physiology↗

bioRxiv2024

Network-based modelling reveals cell-type enriched patterns of non-coding RNA regulation during human skeletal muscle remodelling

A majority of human genes produce non-protein-coding RNA (ncRNA), and some have roles in development and disease. Neither ncRNA nor human skeletal muscle is ideally studied using short-read sequencing, so we used a customised RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies (n=144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growth in vivo, while a transcriptome-driven network model demonstrated interactions via a number of discrete functional pathways and single-cell types. This analysis included established hypertrophy-related ncRNAs, including CYTOR - which was leukocyte-associated (FDR = 4.9 x10-7). Novel hypertrophy-linked ncRNAs included PPP1CB-DT (myofibril assembly genes, FDR = 8.15 x 10-8), and EEF1A1P24 and TMSB4XP8 (vascular remodelling and angiogenesis genes, FDR = 2.77 x 10-5). We also discovered that hypertrophy lncRNA MYREM shows a specific myonuclear expression pattern in vivo. Our multi-layered analyses established that single-cell-associated ncRNA are identifiable from bulk muscle transcriptomic data and that hypertrophy-linked ncRNA genes mediate their association with muscle growth via multiple cell types and a set of interacting pathways. One Sentence SummaryWe used an optimised transcriptomic strategy to identify a set of ncRNA genes regulated during skeletal muscle hypertrophy in one hundred and forty-four people, with network modelling and spatial imaging providing biological context.

bioinformatics↗