Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): How do they work?

Pofi, Riccardo; Gianfrilli, Daniele; Badagliacca, Roberto; Dato, Carla Di; Venneri, Mary Anna; Giannetta, Elisa

doi:10.1007/s40618-015-0339-y

Cited by 26 publications

(17 citation statements)

References 106 publications

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“…Beneficial mechanisms include improved endothelial function, enhanced cGMP and cyclic adenosine monophosphate (cAMP) activity to counterbalance hypertrophic and pro-apoptotic signalling and enhanced post-ischaemic reperfusion. In vitro experiments suggest likely benefits in patients with heart failure [65]. These mechanisms are highlighted in Fig.…”

Section: Evidence That Phosphodiesterase Type 5 Inhibitors Might Redumentioning

confidence: 98%

“…Sildenafil and tadalafil are licensed to treat pulmonary hypertension through their beneficial effects on endothelial dysfunction [3]. Several cardiology reviews have highlighted the beneficial cardiovascular effects that would potentially reduce cardiovascular events in high risk populations such as men with T2DM [3,[65][66][67]. Beneficial mechanisms include improved endothelial function, enhanced cGMP and cyclic adenosine monophosphate (cAMP) activity to counterbalance hypertrophic and pro-apoptotic signalling and enhanced post-ischaemic reperfusion.…”

Section: Evidence That Phosphodiesterase Type 5 Inhibitors Might Redumentioning

confidence: 99%

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Should All Men with Type 2 Diabetes Be Routinely Prescribed a Phosphodiesterase Type 5 Inhibitor?

Hackett

2020

World J Mens Health

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Important health problems in men such as type 2 diabetes (T2DM), insulin resistance, erectile dysfunction, benign prostatic hyperplasia and depression have been shown to have to share common pathological processes, such as endothelial dysfunction and inflammation. This paper discusses the role of phosphodiesterase type 5 (PDE5) inhibitors, through beneficial effects on endothelial function and mediators of chronic inflammation and the possibility to treat or preventing these common conditions. We explore possible barriers to this approach, namely the lack of multiple product licences to treat each of these conditions and how these can be overcome by involving the patient in personalised decisions. We also discuss how opportunities are lost by patients with multiple medical conditions being referred to specialists, primarily interested in one specific problem, with little motivation to treat or prevent conditions outside their remit. We explore how these problems might be related to time and financial restraints or simply a lack of awareness of evidence published in journals related to other specialities. As specialists, we often pride ourselves on providing "personalised" or "patient centred" care, but we can only truly be doing so if we assess the specific needs of the patient across a range of conditions. As part of personalised care in T2DM, we routinely prescribe statins, angiotensin converting enzyme inhibitors and metformin, often with poor compliance. In this paper we explore whether the licensed daily PDE5 inhibitor tadalafil should be added routinely to this list as it will potentially improve and prevent bothersome symptoms and improve compliance with other medications.

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Section: Evidence That Phosphodiesterase Type 5 Inhibitors Might Redumentioning

confidence: 98%

Section: Evidence That Phosphodiesterase Type 5 Inhibitors Might Redumentioning

confidence: 99%

Should All Men with Type 2 Diabetes Be Routinely Prescribed a Phosphodiesterase Type 5 Inhibitor?

Hackett

2020

World J Mens Health

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“…PDE5 inhibitors such as sildenafil, vardenafil and tadalafil are approved for the treatment of erectile dysfunction and pulmonary hypertension but are not yet approved for the treatment of other cardiovascular diseases [ 26 ]. Nevertheless, recent studies suggest potential therapeutic benefits for PDE5 inhibitors, i.e., sildenafil and tadalafil in the treatment of myocardial infarction, ischemia/reperfusion injury, endothelial dysfunction, cardiac hypertrophy and heart failure [ 190 , 191 ].…”

Section: Cyclic Nucleotide Phosphodiesterases (Pdes)mentioning

confidence: 99%

Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

Ercu

Klussmann

2018

JCDD

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A-kinase anchoring proteins (AKAPs) and cyclic nucleotide phosphodiesterases (PDEs) are essential enzymes in the cyclic adenosine 3′-5′ monophosphate (cAMP) signaling cascade. They establish local cAMP pools by controlling the intensity, duration and compartmentalization of cyclic nucleotide-dependent signaling. Various members of the AKAP and PDE families are expressed in the cardiovascular system and direct important processes maintaining homeostatic functioning of the heart and vasculature, e.g., the endothelial barrier function and excitation-contraction coupling. Dysregulation of AKAP and PDE function is associated with pathophysiological conditions in the cardiovascular system including heart failure, hypertension and atherosclerosis. A number of diseases, including autosomal dominant hypertension with brachydactyly (HTNB) and type I long-QT syndrome (LQT1), result from mutations in genes encoding for distinct members of the two classes of enzymes. This review provides an overview over the AKAPs and PDEs relevant for cAMP compartmentalization in the heart and vasculature and discusses their pathophysiological role as well as highlights the potential benefits of targeting these proteins and their protein-protein interactions for the treatment of cardiovascular diseases.

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“…However, its clinical indication has been curtailed because it increases cardiac mortality. 22 Other studies [23][24][25] evaluated the efficacy of PDE5-selective inhibitors, sildenafil and tadalafil, in chronic HF. It is evident from those clinical investigations that depending on morphofunctional impairments and staging of HF, as well as dosing and duration of treatments, the outcome may vary from no significant changes in HR and systolic or diastolic blood pressure 24 to significant improvement of hemodynamics and clinical parameters, even to reversal of maladaptive chamber remodeling.…”

Section: Article See P 120mentioning

confidence: 99%

Phosphodiesterase 2 as a Therapeutic Target for Heart Failure

Chan

2017

Circulation Research

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Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): How do they work?

Abstract: Continuous PDE5 inhibition may exert cardioprotective effects, improving endothelial function and counteracting cardiac remodeling in some but not all conditions. A better patient selection could help to clarify the controversies on PDE5i use for CV disorders.

Cited by 26 publications

References 106 publications

Should All Men with Type 2 Diabetes Be Routinely Prescribed a Phosphodiesterase Type 5 Inhibitor?

Should All Men with Type 2 Diabetes Be Routinely Prescribed a Phosphodiesterase Type 5 Inhibitor?

Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

Phosphodiesterase 2 as a Therapeutic Target for Heart Failure

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