Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating AMP-activated protein kinase.
BACKGROUND
Mesenchymal stem cells (MSCs) are the optimal candidate of treating myocardial infarction; however, the lower survival ratio of implanted cell discourages the advantages of this treatment. Recent studies have displayed statins, which exert pleiotropic effects on the cardiovascular system partially through the increase in endothelial nitric oxide synthase (eNOS) activity, could increase the livability of cells under hypoxia and serum-free (H/SF) conditions. AMP-activated protein kinase (AMPK) is the essential part in keeping the balance of energy production and metabolism in various tissues, which is the dominant factor modulating the programmed cell death. Therefore, we hypothesized that atorvastatin could protect MSCs from H/SF injury through AMPK-eNOS pathway.


RESULTS
Stained with Annexin V/propidine iodine (PI), we found atorvastatin (0.001 μM-10 μM) reduced apoptosis of porcine bone marrow-derived MSCs cultured in H/SF condition; however, this effect was obstructed by compound C, an inhibitor of AMPK. This trend was similar as what bax protein, a pro-apoptosis protein, showed analyzed by Western blotting; whereas the bcl-2 protein, an anti-apoptosis protein, increased in atorvastatin treated cells. Meanwhile, MSCs treated with atorvastatin increased phosphorylation of AMPK and eNOS. The uptrend was partially inhibited by compound C.


CONCLUSIONS
Atorvastatin can activate AMPK and the phosphorylation of AMPK results in eNOS activated, which provides a novel explanation for the multi-effect of statins on cardiovascular system.
Dong
Qiuting
Q
Department of Cardiology, FuWai Hospital and Cardiovascular Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 Beilishi Rd, Beijing 100037, People's Republic of China.
Yang
Yuejin
Y
Song
Lei
L
Qian
Haiyan
H
Xu
Zhimin
Z
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000069059:Atorvastatin; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology*; D011758:Pyrroles / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature
D016895:Culture Media, Serum-Free; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D055372:AMP-Activated Protein Kinases