Abstract

The cardiac endothelium is formed by a continuous monolayer of cells that line the cavity of the heart (endocardial endothelial cells (EECs)) and the luminal surface of the myocardial blood vessels (intramyocardial capillary endothelial cells (IMCEs)). EECs and IMCEs can exercise substantial control over the contractility of cardiomyocytes by releasing various factors such as nitric oxide (NO) via a constitutive endothelial NO-synthase (eNOS), endothelin-1, prostaglandins, angiotensin II, peptide growth factors, and neuregulin-1. The purpose of the present paper is actually to shortly review recent new information concerning cardiomyocytes as effectors of endothelium paracrine signaling, focusing particularly on contractile function. The modes of action and the regulatory paracrine role of the main mediators delivered by cardiac endothelial cells upon cardiac contractility identified in cardiomyocytes are complex and not fully described. Thus, careful evaluation of new therapeutic approaches is required targeting important physiological signaling pathways, some of which have been until recently considered as deleterious, like reactive oxygen species. Future works in the field of cardiac endothelial cells and cardiac function will help to better understand the implication of these mediators in cardiac physiopathology.

Highlights

  • The purpose of the present review is to shortly review recent new information concerning cardiomyocytes as effectors of endothelium paracrine signaling, focusing on contractile function

  • The modes of action and the regulatory paracrine role of main mediators delivered by cardiac endothelial cells upon cardiac contractility identified in cardiomyocytes are exceedingly complex and are not fully described

  • As pointed out by and fully referenced in Brutsaert [1] “a still higher scale of complexity in the in vivo intact heart may ensue from their interaction with other important cardiomodulatory pathways, such as the β-adrenergic or cholinergic pathways in the heart, atrial and brain natriuretic peptide activity, and circulating thyroid and aldosterone hormones.”

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Summary

Introduction

The purpose of the present review is to shortly review recent new information concerning cardiomyocytes as effectors of endothelium paracrine signaling, focusing on contractile function. It has been shown that statins potentiate eNOS activity by decreasing Cav-1 abundance in vitro and in vivo, at least in macrovascular endothelial cells where the caveolin pool is lower and the proportion of caveolin-bound eNOS is higher [19] (see review in [4]) Another protein called NOSIP (for eNOS-interacting protein) has been described to be able to target eNOS to caveolae in endothelial cells of the cardiac microvasculature in rat heart [20]. The main physiological source of NO in normal, adult nonstressed cardiac tissue is eNOS from EECs and IMCEs. The effects of NO on myocardial contraction and relaxation have been very much studied and the signaling pathways in the heart have been reviewed in detail [4, 24, 25]. ET-1 induces a negative inotropic effect in isolated mouse cardiomyocytes [64]

Prostaglandins
Peptide Growth Factors
Pathophysiological Role of Cardiac Endothelial Cells
Conclusions
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