title: Striated muscle angio-adaptation requires changes in Vasohibin-1 expression pattern.
abstract: Vasohibin-1 (VASH-1) was recently identified as a negative feedback regulator of angiogenesis. Here, we analyzed how the expression of the two active anti-angiogenic VASH-1 isoforms p36 and p42 was altered during physiological and pathological muscle angio-adaptation. Our results showed that VASH-1 protein expression was muscle-type specific, with higher levels detected in less vascularized muscles. In rat plantaris and heart muscles, the expression of VASH-1 protein was decreased in response to exercise training, a physiological pro-angiogenic stimulus leading to muscle capillary growth. Interestingly, expression patterns for p36 and p42 were different between plantaris and heart muscles. Next, we analyzed the time-course expression of VASH-1 isoforms in rat soleus muscles subjected to hindlimb unloading, a model that induces muscle capillary regression. Both p36 and p42 isoforms were increased, a signal in favor of some vessel destabilization and regression. Finally, we investigated VASH-1 expression in plantaris muscles from Zucker Diabetic Fatty rats (ZDF) that develop obesity and type-2 diabetes associated with a loss of capillaries in skeletal muscle. VASH-1 expression was higher in sedentary ZDF rats when compared to lean animals, suggesting its potential role during capillary regression. Interestingly, a physiological VASH-1 level was efficiently restored in spontaneously active ZDF animals where muscle capillarization was preserved. In conclusion, our results bring evidence that endogenous VASH-1 isoforms p36 and p42 are key actors of physiological and pathological muscle angio-adaptation.
authors.affiliation: York University, Faculty of Health, Muscle Health Research Center, Toronto, ON, Canada.
authors.forename: Marina
authors.initials: M
authors.lastname: Kishlyansky
authors.forename: Jovana
authors.initials: J
authors.lastname: Vojnovic
authors.forename: Emilie
authors.initials: E
authors.lastname: Roudier
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gineste
authors.forename: Simon
authors.initials: S
authors.lastname: Decary
authors.forename: Paul
authors.initials: P
authors.lastname: Forn
authors.forename: Raynald
authors.initials: R
authors.lastname: Bergeron
authors.forename: Dominique
authors.initials: D
authors.lastname: Desplanches
authors.forename: Olivier
authors.initials: O
authors.lastname: Birot
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002196:Capillaries / Q000254:growth & development; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D054792:Muscle, Striated / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
chemical_list: D018797:Cell Cycle Proteins; D020033:Protein Isoforms; C552060:VASH1 protein, rat