Abnormal Flow Conditions Promote Endocardial Fibroelastosis Via Endothelial-to-Mesenchymal Transition, Which Is Responsive to Losartan Treatment

Abstract

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Case report: Active clinical manifestation of endocardial fibroelastosis in adolescence in a patient with mitral and aortic obstruction–histologic presence of endothelial-to-mesenchymal transformation

“…Endothelial-to-mesenchymal transformation can be induced by different stimuli including mechanical forces or inflammation ( 12 ). As we have previously shown hemodynamic alterations, primarily flow disturbances are directly associated with the induction of EndMT ( 5 – 7 ). Flow disturbances had been present in this patient since birth.…”

“…Hypothetically, EFE can prevent normal growth and development of the LV but potentially might also contribute to the pathologic changes of the MV and LVOT and aortic valve. We have also recently reported that flow disturbances are associated with the remodeling of the endocardium through a process called endothelial-to-mesenchymal transformation (EndMT), which we have shown as an underlying root cause for EFE formation (5)(6)(7). EndMT is the phenotypical switch of endocardial endothelial cells to mesenchymal cells which is a normal developmental process during fetal heart morphogenesis giving rise to the septa and valves (8).…”

The value of cardiac magnetic resonance imaging in endocardial fibroelastosis

“…Left ventricular dysfunction caused by EFE sometimes causes fulminant progression to heart failure. Early diagnosis, early treatment, and long-term adherence are the key to a good prognosis ( 13 ). Histological examination remains the “gold standard” for EFE diagnosis.…”

The Role of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

“…In addition, endothelial-specific deletion of fibroblast growth factor receptor substrate 2 (FRS2) results in extensive EndoMT in the atherosclerotic plaque, which is accompanied by increased fibronectin deposition and neointima formation [ 105 ]. TGFβ signaling and transcription factor Snail were shown in response to shear stress, and the activated ECs initiated inflammatory responses via EndoMT in atherosclerosis [ 124 ]. Consistently, endothelial-specific TGFβRI/TGFβRII knockout in murine models of atherosclerosis has been shown to limit EndoMT, decrease inflammatory responses and plaque progression, and even enable plaque regression [ 31 , 85 , 125 ].…”

“…Preclinical studies of inhibitors majorly focus on fibrosis complications through EndoMT. For example, hepatocyte growth factor, losartan, scutellarin, BMP-7, and relaxin have been demonstrated to repress EndoMT and attenuate cardiac fibrosis [ 96 , 124 , 147 , 148 , 149 , 150 ]. These inhibitors of EndoMT could be therapeutic candidates for treating other diseases where EndoMT occurs and contributes to the pathogenesis.…”