Abstract
Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either
secondary to coronary artery disease or from a distinct entity known as “diabetic
cardiomyopathy.” Furthermore, heart failure with preserved ejection fraction (HFpEF)
is emerging as a significant clinical problem for patients with DM. Current clinical
data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical
structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased
interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along
with advanced glycation end products deposition. There is a myriad of mechanisms that
result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate
utilization, altered insulin signalling leading to protein kinase C activation, advanced
glycated end products deposition, prosclerotic cytokine activation (eg, transforming
growth factor-β activation), along with impaired nitric oxide production from the
endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte
interactions. Despite intense research, current therapeutic strategies have had little
effect on improving morbidity and mortality in patients with DM and HFpEF. Possible
explanations for this include a limited understanding of the role that direct cell-cell
communication or indirect cell-cell paracrine signalling plays in the pathogenesis
of DM and HFpEF. Additionally, integrins remain another important mediator of signals
from the extracellular matrix to cells within the failing heart and might play a significant
role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms
of DM and HFpEF to stimulate potential future research for patients with this common,
and morbid condition.
Résumé
Le diabète est une cause majeure d'insuffisance cardiaque dans les pays occidentaux,
qu'il soit consécutif à une coronaropathie ou attribuable à une entité clinique distincte
appelée « cardiomyopathie diabétique ». De plus, l'insuffisance cardiaque à fraction
d'éjection préservée (ICFEP) est un nouveau problème clinique de plus en plus important
chez les patients atteints de diabète. D'après les données cliniques actuelles, de
30 à 40 % des patients atteints d'ICFEP sont diabétiques. La dysfonction endothéliale,
l'intensification de la fibrose interstitielle et périvasculaire, la rigidité et l'hypertrophie
des cardiomyocytes et le dépôt de produits de la glycation avancée constituent le
phénotype structurel caractéristique du cœur dans l'ICFEP. Il existe une multitude
de mécanismes qui aboutissent à l'apparition du phénotype du coeur ICFEP, y compris
l'altération du métabolisme cardiaque et de l'utilisation des substrats, l'altération
de la signalisation insulinique menant à l'activation de la protéine kinase C, le
dépôt de produits de la glycation avancée, l'activation de la cytokine prosclérotique
(p. ex., activation du facteur de croissance transformant β), et l'altération de la
production d'oxyde nitrique dans l'endothélium. De plus, des études récentes ont porté
sur le rôle des interactions entre cellules endothéliales et myocytes. Malgré des
recherches intensives, les stratégies thérapeutiques actuelles se sont avérées peu
efficaces pour améliorer la morbidité et la mortalité chez les patients diabétiques
atteints d'ICFEP. Cette situation pourrait notamment s'expliquer par notre compréhension
incomplète du rôle joué par la communication directe cellule-cellule et la signalisation
paracrine dans la pathogenèse du diabète et de l'ICFEP. De plus, l'intégrine demeure
un autre médiateur important des signaux de la matrice extracellulaire vers les cellules
dans le cœur insuffisant et pourrait jouer un rôle important dans le dialogue entre
les cellules. Dans cette revue, nous présentons les caractéristiques et les mécanismes
du diabète et de l'ICFEP afin de stimuler les recherches futures dans l’intérêt des
patients atteints de cette affection fréquente et invalidante.
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Article info
Publication history
Published online: March 01, 2018
Accepted:
February 25,
2018
Received:
February 13,
2018
Footnotes
See page 639 for disclosure information.
Identification
Copyright
© 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
