miR-208a as a biomarker of isoproterenol-induced cardiac injury in Sod2+/- and C57BL/6J wild-type mice.
This investigation examined microRNA-208a (miR-208a) as a potential biomarker of isoproterenol (ISO)-induced cardiac injury in superoxide dismutase-2 (Sod2(+/-) ) and the wild-type mice, and the potential sensitivity of Sod2(+/-) mice to ISO-induced toxicity. A single intraperitoneal injection of ISO was administered to age-matched wild-type and Sod2(+/-) mice at 0, 80, or 160 mg/kg. Plasma miR-208a, cardiac troponin I (cTnI), and ISO systemic exposure were measured at various time points postdose. Hearts were collected for histopathology examination and for tissue expression of miR-208a and myosin heavy chain 7. ISO administration caused increases in cTnI and miR-208a plasma levels that correlated with myocardial damage; however, the magnitude of increase differed according to the types of mice. At similar ISO systemic exposure, the magnitude of cTnI was greater in wild-type mice compared to Sod2(+/) (-) mice; however, the magnitude of miR-208a was greater in Sod2(+/-) mice than that of the wild-type mice. Myocardial degeneration occurred at ≥3 hr in the wild-type and ≥6 hr in Sod2(+/) (-) mice. At ≥24 hr after ISO administration, miR-208a appeared superior to cTnI in indicating myocardial injury in both wild-type and Sod2(+/-) mice. Sod2(+/-) mice were not more sensitive than wild-type mice to ISO-induced toxicity.
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA ling.liu@pfizer.com.
Ling
L
Liu
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Shirley A
SA
Aguirre
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Winston E N
WE
Evering
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Brad P
BP
Hirakawa
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Jeffrey R
JR
May
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Kimbie
K
Palacio
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Jianying
J
Wang
Pfizer Global Research and Development, Bioanalytical Research, Groton, Connecticut, USA.
Yizhong
Y
Zhang
Pfizer Global Research and Development, Drug Safety Research and Development, San Diego, California, USA.
Gregory J
GJ
Stevens
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D024722:Cardiac Myosins / Q000097:blood; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood*; D018995:Myosin Heavy Chains / Q000097:blood; D013482:Superoxide Dismutase / Q000378:metabolism; D019210:Troponin I / Q000097:blood; D000099156:Superoxide Dismutase 2
D015415:Biomarkers; D024722:Cardiac Myosins; D053148:Caspase 3; D007545:Isoproterenol; D035683:MicroRNAs; D018995:Myosin Heavy Chains; D013482:Superoxide Dismutase; D019210:Troponin I; D000099156:Superoxide Dismutase 2; C543978:Mirn208 microRNA, mouse; C505409:Casp3 protein, mouse
cTnI; cardiac toxicity.; isoproterenol; miR-208a; mouse