Author + information
- Ramesh C. Gupta,
- Kristina Szekely,
- Mengjun Wang,
- Kefei Zhang,
- Sharad Rastogi,
- Barbara Albrecht-Küpper and
- Hani N. Sabbah
Peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) is an integrator of transcriptional circuits that regulates mitochondrial biogenesis and function. When activated, PGC-1α increases mitochondrial (MITO) oxidative capacity in the heart by increasing MITO number and expression of MITO enzymes. We previously showed that capadenoson (CAP), a partial adenosine A1-receptor agonist, improves LV function in dogs with heart failure (HF). This study examined the effects of CAP on phosphorylation and protein levels of PGC-1α in LV myocardium of HF dogs (LV ejection fraction 30%).
LV tissue from 12 HF dogs randomized to 3 months oral monotherapy with CAP (7.5 mg twice daily, n=6) or to no therapy (HF-Control, n=6) and tissue from 6 normal (NL) dogs was used. Phosphorylated (p-) and total (t-) protein levels of PGC-1α and protein levels of β-actin, an internal control, were measured in LV homogenate by Western blotting.
β-actin was unchanged among study groups. Compared to NL, protein levels of p-PGC-1α and t-PGC-1α and the ratio of p- PGC-1α/t-PGC-1α were significantly reduced in HF-Controls. Therapy with CAP normalized levels of p-PGC-1α and t- PGC-1α and the ratio of p- PGC-1α/t-PGC-1α.
Long-term therapy with CAP improves phosphorylation and total protein level of PGC-1α in LV myocardium of HF dogs. Improved myocardial energetics mediated by Improved PGC-1α regulation may explain the improvement of LV function seen following chronic CAP therapy.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Heart Failure: Pharmacologic Therapy
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 1223-303
- 2013 American College of Cardiology Foundation