Diabetic neuropathy and heart failure: role of neuropeptides

• Published in: Expert reviews in molecular medicine Vol. 13; p. e26
• Main Authors: Ejaz, Asma, LoGerfo, Frank W., Pradhan, Leena
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 10.08.2011
• Subjects: Angiogenesis; Animals; Atrial natriuretic peptide; Autonomic nervous system; Brain natriuretic peptide; C-Type natriuretic peptide; Calcium homeostasis; cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Diabetes; Diabetes mellitus; Diabetic Neuropathies - physiopathology; Heart; Heart diseases; Heart failure; Heart Failure - physiopathology; Heart rate; Humans; Neuropathy; Neuropeptide Y; Neuropeptides - physiology; Peptides; Reviews; Signal transduction; Studies; Substance P; Therapeutic applications; Vasoactive agents
• ISSN: 1462-3994; 1462-3994
• DOI: 10.1017/S1462399411001979

Cardiovascular autonomic neuropathy (CAN), in which patients present with damage of autonomic nerve fibres, is one of the most common complications of diabetes. CAN leads to abnormalities in heart rate and vascular dynamics, which are features of diabetic heart failure. Dysregulated neurohormonal activation, an outcome of diabetic neuropathy, has a significant pathophysiological role in diabetes-associated cardiovascular disease. Key players in neurohormonal activation include cardioprotective neuropeptides and their receptors, such as substance P (SP), neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These neuropeptides are released from the peripheral or autonomic nervous system and have vasoactive properties. They are further implicated in cardiomyocyte hypertrophy, calcium homeostasis, ischaemia-induced angiogenesis, protein kinase C signalling and the renin–angiotensin–aldosterone system. Therefore, dysregulation of the expression of neuropeptides or activation of the neuropeptide signalling pathways can negatively affect cardiac homeostasis. Targeting neuropeptides and their signalling pathways might thus serve as new therapeutic interventions in the treatment of heart failure associated with diabetes. This review discusses how neuropeptide dysregulation in diabetes might affect cardiac functions that contribute to the development of heart failure.