Endothelial Dysfunction in Patients with Severe Mitral Regurgitation.

Benedetta Porro,Paola Canzano,Laura Cavallotti,Marina Camera,Laura Fusini,Paola Gripari,Francesco Alamanni,Linda Turnu,Paola Songia,Donato Moschetta,Paolo Poggio,Veronika A Myasoedova,Vincenza Valerio,Viviana Cavalca

doi:10.3390/jcm8060835

Abstract

Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. It has been reported that MVP patients—candidates for mitral valve repair (MVRep)—showed an alteration in the antioxidant defense systems as well as in the L-arginine metabolic pathway. In this study, we investigate if oxidative stress and endothelial dysfunction are an MVP consequence or driving factors. Forty-five patients undergoing MVRep were evaluated before and 6 months post surgery and compared to 29 controls. Oxidized (GSSG) and reduced (GSH) forms of glutathione, and L-arginine metabolic pathway were analyzed using liquid chromatography-tandem mass spectrometry methods while osteoprotegerin (OPG) through the ELISA kit and circulating endothelial microparticles (EMP) by flow cytometry. Six-month post surgery, in MVP patients, the GSSG/GSH ratio decreased while symmetric and asymmetric dimethylarginines levels remained comparable to the baseline. Conversely, OPG levels significantly increased when compared to their baseline. Finally, pre-MVRep EMP levels were significantly higher in patients than in controls and did not change post surgery. Overall, these results highlight that MVRep completely restores the increased oxidative stress levels, as evidenced in MVP patients. Conversely, no amelioration of endothelial dysfunction was evidenced after surgery. Thus, therapies aimed to restore a proper endothelial function before and after surgical repair could benefit MVP patients.

Highlights

Mitral valve prolapse (MVP) is a debilitating disease afflicting 2% to 3% of people [1,2]
We previously reported that MVP patients with severe regurgitation showed an impairment in the L-arginine (Arg)/nitric oxide (NO) biosynthetic pathway when compared to healthy subjects [13]
The aim of the present study is to investigate if surgical intervention is able to restore, to some extent, the systemic alterations evidenced in MVP patients before surgery, elucidating if oxidative stress and endothelial dysfunction are an MVP consequence or the driving factors

Summary

Introduction

Mitral valve prolapse (MVP) is a debilitating disease afflicting 2% to 3% of people [1,2]. Despite the fact that several studies have evaluated the effectiveness of angiotensin-converting enzyme inhibitors [4,5] and beta-blockers [6,7], no recommended pharmacological therapies for severe mitral regurgitation (MR) with associated MVP have been found. The diagnostic gold standard is two dimensional (2D) echocardiography [8,9,10], whereas surgical intervention is the therapeutic choice when the prolapse causes symptomatic severe regurgitation [11]. The monolayer of valve endothelial cells, covering the entire surface of the leaflets, plays an important role in the homeostasis of the interstitial cells [12]. When endothelial dysfunction occurs, this tight regulation is disrupted, leading to MVP [5,6]

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