Co-Activation of Nuclear Factor-κB and Myocardin/Serum Response Factor Conveys the Hypertrophy Signal of High Insulin Levels in Cardiac Myoblasts
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Why the study?
Does high insulin co-activate NF-κB and myocardin/SRF to convey hypertrophy signaling in cardiac myoblasts?
Population
Canine cardiac myoblasts and 12-month-old wild-type C57BL/6 and Leprdb mice on a C57BL/6 background.
Comparison
High insulin treatment for 0-24 hours, with or… vs Untreated cells, scrambled siRNA, empty vector…
Design
Preclinical
Authors
Discussion
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Implication
May link hyperinsulinemia to hypertrophy via myocardin/NF-κB; leaves open relevance in diabetic cardiomyopathy.
Structured PICO
Does high insulin co-activate NF-κB and myocardin/SRF to convey hypertrophy signaling in cardiac myoblasts?
P
Population
Canine cardiac myoblasts and 12-month-old wild-type C57BL/6 (n=6) and Leprdb (db/db) mice on a C57BL/6 background (n=6).
I
Intervention
High insulin (10^-8 to 10^-7 M) treatment for 0-24 hours, with or without TNF-α, myocardin siRNA, CHIP siRNA, CHIP overexpression, or various inhibitors (LY294002, MG132, PDTC).
C
Comparator
Untreated cells, scrambled siRNA, empty vector, or non-diabetic C57BL/6J control mice.
O
Outcome
Expression of β-myosin heavy chain (MHC), myocardin levels, SRF-SRE binding activity, and NF-κB activation.surrogate
In hyperinsulinemic states, myocardin acts as a nuclear effector of insulin, promoting cardiac hypertrophy through co-activation with NF-κB and SRF.
Cite This Study
Madonna et al. (2014) studied this question.
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