Thrombospondin‐1 protects heart and skeletal muscle mass from cigarette smoke induced modifications

Abstract

Thrombospondin-1 (TSP-1) is a multifunctional extracellular matrix protein that regulates skeletal muscle vascularity, but its involvement in smoking-induced skeletal muscle dysfunction is not well understood. TSP-1 knockout (KO, n=11) and wild-type (WT, n=10) mice were exposed to 20 weeks of cigarette smoke (12 cigarettes over 1 hour each day, 5 days/week). Maximal running speed, using an incremental treadmill exercise test, was measured before and after the 20-week smoke exposure, and every 5-weeks during the exposure. All exercise tests were performed under ambient room air (no smoke) conditions. Upon completion of the smoke exposure period, the soleus, plantaris, gastrocnemius, and heart muscles were excised, weighed as save for morphological and molecular analyses. Maximal running speed was not different between the WT and KO mice prior to smoke, and the decline in performance after smoke exposure was similar between WT and KO. Body mass was not different between WT and KO mice prior to smoke or after smoke exposure. The gastrocnemius and plantaris muscle mass was significantly lower in KO by 10% (160±1 vs. 136±1 mg) and 13% (21.6±0.3 vs. 17.8±0.2 mg), respectively compared to WT mice (p<0.05). No difference in the soleus was seen between KO and WT (9.3±0.1 vs 9.1±0.1 mg, p=n.s.). Heart mass was greater by 13% in KO compared to WT (159±3 vs 1474.67±0.05 mg; respectively, p<0.05). SUMMARY: These data demonstrate that mice lacking TSP-1 have greater loss of skeletal muscle mass and increased cardiac mass compared to WT cigarette smoke exposed mice, suggesting that the actions of TSP-1 may help protect skeletal and cardiac muscle against cigarette smoke induced injury.