Author + information
- Ramesh C. Gupta,
- Kristina Szekely,
- Mengjun Wang,
- Sharad Rastogi,
- Kefei Zhang,
- Barbara Albrecht-Küpper and
- Hani N. Sabbah
Fatty acid (FA) and glucose oxidation are abnormal in heart failure (HF) and contribute to LV dysfunction. FA translocase (FAT/CD36), a protein involved in transmembrane transport of FA, carnitine palmitoyl transferase1b isozyme (CPT1b), a protein involved in transport of FA across the outer mitochondria (MITO) membrane, and citrate synthase (CS), a rate-limiting enzyme in the citric acid cycle, act to regulate FA utilization by MITO. Expression of all 3 proteins is abnormal in the failing LV. We tested the hypothesis that capadenoson (CAP), a partial adenosine A1-receptor agonist shown to improve LV function in HF dogs, normalizes protein levels of CD36, CPT1b, and CS in LV myocardium of HF dogs (LV ejection fraction ∼30%).
LV tissue from 12 HF dogs randomized to 3 months therapy with CAP (7.5 mg twice daily, n=6) or to no therapy (Control, n=6) and tissue from 6 normal (NL) dogs was used. Protein level of CD36 normalized to GAPDH and levels of CPT1b and CS normalized to porin, a MITO protein unchanged in HF, were measured in LV homogenate by Western blotting.
Protein levels of CD36, CPT1b, and CS were reduced in HF-Control compared to NL dogs (Table). Therapy with CAP partially restored levels of all 3 proteins (Table).
In HF dogs, chronic therapy with CAP normalizes expression of proteins involved in myocardial FA oxidation by MITO. The results suggest that CAP normalizes myocardial energy substrate utilization in HF leading to improved myocardial energetics and LV function.
Moderated Poster Contributions
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Heart Failure: Innovations in Medical Therapy
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 1133M-267
- 2013 American College of Cardiology Foundation