Author + information
- Received August 27, 2008
- Revision received January 22, 2009
- Accepted February 19, 2009
- Published online June 2, 2009.
- Osamu Tsukamoto, MD, PhD⁎,‡,
- Masashi Fujita, MD, PhD‡,
- Mahoto Kato, MD⁎,
- Satoru Yamazaki, PhD⁎,
- Yoshihiro Asano, MD, PhD‡,
- Akiko Ogai, PhD⁎,
- Hidetoshi Okazaki, MD, PhD⁎,
- Mitsutoshi Asai, MD‡,
- Yoko Nagamachi, BS‡,
- Norikazu Maeda, MD, PhD§,
- Yasunori Shintani, MD, PhD‡,
- Tetsuo Minamino, MD, PhD‡,
- Masanori Asakura, MD, PhD⁎,
- Ichiro Kishimoto, MD, PhD†,
- Tohru Funahashi, MD, PhD§,
- Hitonobu Tomoike, MD, PhD⁎ and
- Masafumi Kitakaze, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Masafumi Kitakaze, Department of Cardiovascular Medicine, National Cardiovascular Center, Suita, Osaka 565-8565, Japan
Objectives We investigated the functional relationship between natriuretic peptides and adiponectin by performing both experimental and clinical studies.
Background Natriuretic peptides are promising candidates for the treatment of congestive heart failure (CHF) because of their wide range of beneficial effects on the cardiovascular system. Adiponectin is a cytokine derived from adipose tissue with various cardiovascular-protective effects that has been reported to show a positive association with plasma brain natriuretic peptide (BNP) levels in patients with heart failure.
Methods The expression of adiponectin messenger ribonucleic acid (mRNA) and its secretion were examined after atrial natriuretic peptide (ANP) or BNP was added to primary cultures of human adipocytes in the presence or absence of HS142-1 (a functional type A guanylyl cyclase receptor antagonist). Changes of the plasma adiponectin level were determined in 30 patients with CHF who were randomized to receive intravenous ANP (0.025 μg/kg/min human ANP for 3 days, n = 15) or saline (n = 15).
Results Both ANP and BNP dose-dependently enhanced the expression of adiponectin mRNA and its secretion, whereas such enhancement was inhibited by pre-treatment with HS142-1. The plasma adiponectin level was increased at 4 days after administration of human ANP compared with the baseline value (from 6.56 ± 0.40 μg/ml to 7.34 ± 0.47 μg/ml, p < 0.05), whereas there was no change of adiponectin in the saline group (from 6.53 ± 0.57 μg/ml to 6.55 ± 0.56 μg/ml).
Conclusions Natriuretic peptides enhance adiponectin production by human adipocytes in vitro and even in patients with CHF, which might have a beneficial effect on cardiomyocytes in patients receiving recombinant natriuretic peptide therapy for heart failure.
This work is supported by grants-in-aid from the Ministry of Health, Labor, and Welfare-Japan, grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology-Japan, grants from the Japan Heart Foundation, and grants from the Japan Cardiovascular Research Foundation (all to Dr. Kitakaze) and Takeda Medical Research Foundation (to Dr. Funahashi). Drs. Tsukamoto, Fujita, and Kato contributed equally to this work.
- Received August 27, 2008.
- Revision received January 22, 2009.
- Accepted February 19, 2009.
- American College of Cardiology Foundation