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Cardiovascular Autonomic Neuropathy in Diabetes

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Diabetic Cardiomyopathy

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 9))

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Abstract

The heart is extensively innervated, and its electrical and mechanical performance is controlled by the autonomic nervous system. The cardiac nervous system comprises the sympathetic, parasympathetic, and sensory nervous systems that together regulate heart function on demand. The density of cardiac innervation varies in diseased hearts, leading to unbalanced neural activation and lethal arrhythmia. Diabetic sensory neuropathy causes silent myocardial ischemia, which is characterized by loss of pain perception during myocardial ischemia and is a major cause of sudden cardiac death in diabetes mellitus (DM). Despite its clinical importance, the mechanisms underlying the control and regulation of cardiac innervation remain poorly understood. Nerve growth factor (NGF), a potent chemoattractant, is highly expressed in cardiomyocytes during development. In contrast, Sema3a, a neural chemorepellent, is highly expressed in the subendocardium of early-stage embryos, but is suppressed during development. The balance between NGF and Sema3a expression leads to epicardial to endocardial transmural sympathetic innervation patterning. Downregulation of NGF leads to diabetic neuropathy, whereas NGF supplementation rescues silent myocardial ischemia in DM. In this review, we summarize the molecular mechanisms underlying cardiac autonomic innervation, with a particular focus on DM and the clinical implications of cardiac autonomic neuropathy.

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Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Takahide Arai, Masaki Ieda & Keiichi Fukuda

  2. Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Keiichi Fukuda

Authors
  1. Takahide Arai
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  2. Masaki Ieda
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  3. Keiichi Fukuda
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Corresponding author

Correspondence to Keiichi Fukuda .

Editor information

Editors and Affiliations

  1. Department of Biophysics, University of Ankara, Ankara, Ankara, Turkey

    Belma Turan

  2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Arai, T., Ieda, M., Fukuda, K. (2014). Cardiovascular Autonomic Neuropathy in Diabetes. In: Turan, B., Dhalla, N. (eds) Diabetic Cardiomyopathy. Advances in Biochemistry in Health and Disease, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9317-4_14

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