An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction.
Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate--the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs.
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
Motoaki
M
Murakoshi
Kyohei
K
Saiki
Kyoji
K
Urayama
Thomas N
TN
Sato
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D011774:Pyrvinium Compounds / Q000494:pharmacology* / Q000627:therapeutic use
D000871:Anthelmintics; D011774:Pyrvinium Compounds; C024631:pyrvinium