Cardiovascular autonomic neuropathy in diabetes

Takahide Arai, Masaki Ieda, Keiichi Fukuda

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish
Title of host publicationDiabetic Cardiomyopathy
Subtitle of host publicationBiochemical and Molecular Mechanisms
PublisherSpringer New York
Pages239-248
Number of pages10
ISBN (Electronic)9781461493174
ISBN (Print)9781461493167
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Nerve Growth Factor
Medical problems
Neurology
Semaphorin-3A
Myocardial Ischemia
Diabetes Mellitus
Diabetic Neuropathies
Parasympathetic Nervous System
Pain Perception
Autonomic Nervous System
Sudden Cardiac Death
Chemotactic Factors
Sympathetic Nervous System
Cardiac Myocytes
Cardiac Arrhythmias
Heart Diseases
Down-Regulation
Embryonic Structures
Chemical activation

Keywords

  • Autonomic neuropathy
  • Cardiac nervous system
  • Diabetes mellitus
  • Nerve growth factor
  • Sema3a

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Arai, T., Ieda, M., & Fukuda, K. (2014). Cardiovascular autonomic neuropathy in diabetes. In Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms (pp. 239-248). Springer New York. https://doi.org/10.1007/978-1-4614-9317-4_14

Cardiovascular autonomic neuropathy in diabetes. / Arai, Takahide; Ieda, Masaki; Fukuda, Keiichi.

Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms. Springer New York, 2014. p. 239-248.

Research output: Chapter in Book/Report/Conference proceedingChapter

Arai, T, Ieda, M & Fukuda, K 2014, Cardiovascular autonomic neuropathy in diabetes. in Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms. Springer New York, pp. 239-248. https://doi.org/10.1007/978-1-4614-9317-4_14
Arai T, Ieda M, Fukuda K. Cardiovascular autonomic neuropathy in diabetes. In Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms. Springer New York. 2014. p. 239-248 https://doi.org/10.1007/978-1-4614-9317-4_14
Arai, Takahide ; Ieda, Masaki ; Fukuda, Keiichi. / Cardiovascular autonomic neuropathy in diabetes. Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms. Springer New York, 2014. pp. 239-248
@inbook{26d614dd7441469b8c9157c2f9118a46,
title = "Cardiovascular autonomic neuropathy in diabetes",
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.",
keywords = "Autonomic neuropathy, Cardiac nervous system, Diabetes mellitus, Nerve growth factor, Sema3a",
author = "Takahide Arai and Masaki Ieda and Keiichi Fukuda",
year = "2014",
month = "1",
day = "1",
doi = "10.1007/978-1-4614-9317-4_14",
language = "English",
isbn = "9781461493167",
pages = "239--248",
booktitle = "Diabetic Cardiomyopathy",
publisher = "Springer New York",
address = "United States",

}

TY - CHAP

T1 - Cardiovascular autonomic neuropathy in diabetes

AU - Arai, Takahide

AU - Ieda, Masaki

AU - Fukuda, Keiichi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Autonomic neuropathy

KW - Cardiac nervous system

KW - Diabetes mellitus

KW - Nerve growth factor

KW - Sema3a

UR - http://www.scopus.com/inward/record.url?scp=85028505651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028505651&partnerID=8YFLogxK

U2 - 10.1007/978-1-4614-9317-4_14

DO - 10.1007/978-1-4614-9317-4_14

M3 - Chapter

SN - 9781461493167

SP - 239

EP - 248

BT - Diabetic Cardiomyopathy

PB - Springer New York

ER -