Role of endothelial dysfunction in heart failure

  • Cinzia Zuchi
  • Isabella Tritto
  • Erberto Carluccio
  • Cristian Mattei
  • Gaia Cattadori
  • Giuseppe AmbrosioEmail author


Coronary artery disease is a major underlying etiology for heart failure. The role of coronary microvascular disease, and endothelial dysfunction, in the pathophysiology of heart failure is poorly appreciated. Endothelial dysfunction, induced by oxidative stress, contributes to the development of heart failure. Alterations of endothelial function and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway are involved in the pathophysiology of heart failure with both reduced and preserved ejection fraction. Indeed, an altered endothelium dependent vasodilatation, causing repeated episodes of ischemia/reperfusion, can induce a chronic stunned myocardium with systolic dysfunction and an increased diastolic stiffness with diastolic dysfunction. Moreover, the altered NO-cGMP pathway directly affects myocardial homeostasis. Endothelial dysfunction is associated with worse prognosis and higher rate of cardiovascular events. Potential therapeutic strategies targeting the NO-cGMP pathway in patients with HF will be discussed in this review article. Although clinical data are still inconclusive, the NO-cGMP pathway represents a promising target for therapy.


Heart failure Endothelial dysfunction Nitric oxide Microcirculation 


Funding information

This paper did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Cardiology and Cardiovascular PathophysiologyAzienda Ospedaliero-Universitaria “S. Maria della Misericordia”PerugiaItaly
  2. 2.MultiMedica IRCCSMilanItaly
  3. 3.Department of CardiologyOspedale S. Maria della Misericordia Piazzale Menghini, 1PerugiaItaly

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