Background
Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, and is a primary risk factor for chronic heart failure. The main symptom in patients with heart failure is exercise intolerance, but this is poorly correlated with cardiac dysfunction. In contrast, heart failure is commonly associated with skeletal muscle pathology that is closely linked to worse symptoms. However, the underlying mechanisms remain poorly defined. Skeletal muscle health is maintained by a population of quiescent muscle stem cells (MuSCs), but their role in heart failure-induced muscle pathology remains poorly explored.
Methods
We studied a mouse model of heart failure 4 weeks following MI surgery after ligation of the left coronary artery (n=7) compared to sham controls (n=4) in 15-week-old C57Bl6 females. To assess whether MuSCs were dysregulated post MI, fluorescent activated cell sorting (FACS) was used to isolate VCAM1+/α7-Integrin+/CD31–/CD45–/Sca1– MuSCs from hindlimb muscles. Populations of CD31+ endothelial cells, CD45+ hematopoietic cells, and Sca1+ fibro/adipogenic progenitors were also characterised.
Results
Pathological cardiac remodelling was confirmed via in vivo echocardiography (left ventricular ejection fraction <40 %) and stained ventricular cryosections (infarction size >20%). Hindlimb muscle mass was 10 % lower (p=0.019) in mice with heart failure compared to controls (308±23 vs 344±13 mg, respectively). Moreover, isolated muscle fibre bundles showed overt weakness when stimulated maximally in vitro (27±3 vs. 16±2 N/cm2) (p<0.001). Total isolated MuSCs were higher (p=0.002) in mice with heart failure compared to controls (3.4±0.5 vs. 2.3±0.4 %, respectively). The percentage of endothelial, haematopoietic and fibro/adipogenic progenitor cells were not different between groups (p>0.05)
Conclusion
These preliminary data indicate that heart failure may influence MuSC properties, but whether they contribute towards to the observed muscle pathology requires further investigation.