Macrophage involvement in mitral valve pathology in mucopolysaccharidosis type VI (Maroteaux–lamy syndrome)

Abstract

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is a rare lysosomal storage disorder in which the pathologic storage of glycosaminoglycans in various tissues can lead to severe symptoms, including cardiomyopathy. We report on a child with Maroteaux-Lamy syndrome whose cardiac condition deteriorated and eventually led to cardiac failure at the age of 7 years due to severe mitral regurgitation. She received a mitral valve replacement and tricuspid repair with successful outcome. Histologic examination of the mitral valve showed abundant "clear" cells in both the leaflets and chordae tendineae. In Hurler disease (MPS I), similar cells have been identified as activated valvular interstitial cells (VICs, a myofibroblast like cell type). Here we report that the "clear" cells are CD68 positive, a frequently used marker of macrophage lineage. The "clear" cells remained unstained with the more specific macrophage marker CD14 while persistent staining of other cells demonstrated macrophage infiltration. From these observations, we infer that macrophages are involved in mitral valve pathology in MPS VI.

Perthes-Like Disease Masquerading Non-Classical MPS

“…Interestingly, dermatan sulphate is the most predominant GAG found in cardiac valve connective tissues and blood vessels. Thus, this GAG accumulation can progressively promote thickening and deformation of valves [22,23].…”

Surgical Management of Valvular Heart Disease in Mucopolysaccharidoses: A Review of Literature

“…In valvular interstitial cells, which normally are responsible for valve growth and repair, MPS leads to activation and development of large, GAG-laden “Hurler” cells [ 28 ]. Additionally, an inflammatory and macrophage response is induced, causing further tissue dysfunction [ 29 ]. These GAG-triggered processes lead to valve thickening, diminished leaflet mobility, and coaptation deficiency.…”

The second genome: Effects of the mitochondrial genome on cancer progression

“…Several studies using MNX mice have implicated that mtDNA (in) directly influences the immune system. Fetterman et al used MNX mice with C57BL/6J and C3H/HeN genetic backgrounds to test mtDNA impacts on atherosclerosis and cardiac valve regurgitation (Fetterman et al, 2013), both pathologies which have been associated with macrophage infiltration (Brands et al, 2013). ROS production and membrane polarization in cardiomyocytes or mice harboring C57BL/6J mtDNA were more susceptible to both phenotypes than cells/mice containing C3H/HeN mtDNA (Table 1) (Fetterman et al, 2013).…”