doi: 10.1161/CIRCRESAHA.108.191122
© 2009 American Heart Association, Inc.
Editorials |
Serotonin 5-HT2B Receptor in Cardiac Fibroblast Contributes to Cardiac Hypertrophy
A New Therapeutic Target for Heart Failure?
From the Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei; and Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan.
Correspondence to Dr Kou-Gi Shyu, Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang RD, Taipei 111, Taiwan. E-mail shyukg@ms12.hinet.net
See related article, pages 113–123
Key Words: cardiac hypertrophy • serotonin receptor • cardiac fibroblast • isoproterenol
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Cardiac hypertrophy is often accompanied by cardiac remodeling characterized by loss of cardiac myocytes, interstitial fibroblasts, and collagen deposition, leading to decreased ventricular compliance and an increased risk for heart failure. The mortality for patients with heart failure is still high, although some improvements have been demonstrated in patients with systolic heart failure.1–3 To improve the therapeutic strategy for patients with heart failure, especially diastolic heart failure, further research and investigations to better understand the molecular and biochemical mechanism are needed.
Serotonin (5-hydroxytryptamine [5-HT]) affects many physiological functions through the interaction with specific G-coupled membrane receptors, 5-HT receptors. There are 4 classes of 5-HT receptors (5-HT1/5, 5-HT2, 5-HT3, and 5-HT4/6/7).4 Serotonin, via the 5-HT2B receptor, regulates cardiac development and function.5 Transgenic mice with a 5-HT2B receptor gene ablation show embryonic and neonatal death caused by lack of trabeculae in the heart.6 5-HT2B receptors are essential for isoproterenol-induced cardiac hypertrophy, which involves the regulation of interleukin-6, interleukin-1β, and tumor necrosis factor-
cytokine production by cardiac fibroblasts.7 The 5-HT2B receptor has been shown functionally coupled to reactive oxygen species synthesis through NAD(P)H oxidase stimulation in neuronal cells8 and in angiotensin II and isoproterenol-induced cardiac hypertrophy.9 Recently, 5-HT2B receptor blockade has been shown to prevent the cardiac hypertrophy induced by angiotensin II or isoproterenol infusion.9 The 5-HT2B receptor has also been shown to be involved in cardiac hypertrophy by acting directly on cardiac myocytes.10 Serotonin plasma level and serotonin activity are increased in patients with heart failure and in
Related Article:
Circ. Res. 2009 104: 113-123.