Proinflammatory Matrix Metalloproteinase-1 Associates With Mitral Valve Leaflet Disruption Following Percutaneous Mitral Valvuloplasty

Abstract

Mitral regurgitation (MR) is a major complication of the percutaneous mitral valvuloplasty (PMV). Despite high technical expertise and cumulative experience with the procedure, the incidence rate of severe MR has not decreased. Although some of MR can be anticipated by echocardiographic analysis; leaflet tearing, which leads to the most dreaded type of MR, remains unpredictable. Irregular valvular collagen remodeling is likely to compromise tissue architecture and increase the tearing risk during PMV balloon inflation. In this study, we evaluated histological and molecular characteristics of excised mitral valves from patients with rheumatic mitral stenosis (MS) who underwent emergency surgery after PMV due to severe MR caused by leaflet tear. Those findings were compared with patients who underwent elective mitral valve replacement surgery owing to severe MS, in whom PMV was not indicated. In vitro assay using peripheral blood mononuclear cells was performed to better understand the impact of the cellular and molecular alterations identified in leaflet tear mitral valve specimens. Our analysis showed that focal infiltration of inflammatory cells contributes to accumulation of MMP-1 and IFN-γ in valve leaflets. Moreover, we showed that IFN-γ increase the expression of MMP-1 in CD14+ cells (monocytes) in vitro. Thus, inflammatory cells contribute to unevenly remodel collagen resulting in variable thickening causing abnormalities in leaflet architecture making them more susceptible to laceration.

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

“…This may have an implication for myocardial remodelling and fibrosis during this condition [ 114 ]. Regarding rheumatic heart disease, despite several works found an increased expression of MMP-1 and MMP-9 in the mitral valve [ 115 ] and/or serum [ 116 , 117 , 118 ] of patients compared to controls, correlated with the underlying inflammation, there is currently no single study that explored a possible influence of sex on MMP expression. Sex-related differences in MMPs in patients affected by CVDs are summarized in Table 3 .…”

The role of monocytes in thrombotic diseases: a review

“…Left atrial (LA) thrombosis is a common complication with RHD and mitral stenosis (MS) (241). As early as 1991, the luminol-enhanced chemiluminescence technique was used to study the production of oxygen free radicals (OFR) by monocytes and neutrophils in the peripheral blood of patients with RF and RHD (242). It has been observed that in RHD patients, phagocytes are capable of penetrating the myocardium and possibly contributing to the development of cardiac injury by generating OFR (242).…”

“…As early as 1991, the luminol-enhanced chemiluminescence technique was used to study the production of oxygen free radicals (OFR) by monocytes and neutrophils in the peripheral blood of patients with RF and RHD (242). It has been observed that in RHD patients, phagocytes are capable of penetrating the myocardium and possibly contributing to the development of cardiac injury by generating OFR (242). In a clinical study of mitral valve resection in patients with rheumatic MS, histological studies have revealed a positive correlation between the degree of infiltration of inflammatory cells in valve tissue and the levels of MMP-1 and IFN-γ.…”