Clear cells in the atrioventricular valves of infants with severe human mucopolysaccharidosis (Hurler syndrome) are activated valvular interstitial cells

Braunlin, Elizabeth; Tolar, Jakub; Mackey-Bojack, Shannon; Masinde, Tiwanda; Krivit, William; Schoen, Frederick J.

doi:10.1016/j.carpath.2010.06.004

« Previous Next »Cardiovascular Pathology
Volume 20, Issue 5 , Pages 315-321, September 2011

Clear cells in the atrioventricular valves of infants with severe human mucopolysaccharidosis (Hurler syndrome) are activated valvular interstitial cells

Elizabeth Braunlin
- Department of Pediatrics, University of Minnesota Hospital/Fairview, Minneapolis, MN, USA
- Corresponding author. Department of Pediatrics, University of Minnesota Hospital/Fairview, MMC 94, Minneapolis, MN 55455, USA. Tel.: +1 612 626 2755; fax: +1 612 626 2467.
Jakub Tolar
- Department of Pediatrics, University of Minnesota Hospital/Fairview, Minneapolis, MN, USA
Shannon Mackey-Bojack
- The Jesse E. Edwards Registry of Cardiovascular Disease, St. Paul, MN, USA
Tiwanda Masinde
- Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
William Krivit
- Department of Pediatrics, University of Minnesota Hospital/Fairview, Minneapolis, MN, USA
- Deceased.
Frederick J. Schoen
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

Received 18 February 2010; received in revised form 6 May 2010; accepted 2 June 2010. published online 12 July 2010.

Abstract

Background

Severe mucopolysaccharidosis type I (Hurler syndrome) is an autosomal recessive lysosomal storage disease of childhood that results in accumulation of glycosaminoglycans within cardiac valves and consequent valve dysfunction. Valve thickening in mucopolysaccharidosis type I (Hurler syndrome) is due, in part, to the presence of glycosaminoglycan-laden cells (the so-called “clear” or “Hurler” cells) within the valve that remain largely unstudied with respect to identity, origin, and function. We hypothesized that the “clear” or “Hurler” cells within the atrioventricular valves from individuals with untreated mucopolysaccharidosis type I are activated valvular interstitial cells.

Methods

We performed routine and immunohistochemical staining on atrioventricular valves from two infants with untreated severe mucopolysaccharidosis type I (Hurler syndrome) and compared them to atrioventricular valve tissue from two age-matched and gender-matched normal infants.

Results

Despite the marked differences in their histological appearances, mucopolysaccharidosis type I valve cells have an immunohistochemical fingerprint identical to that of normal infant valvular interstitial cells. Both mucopolysaccharidosis type I valvular interstitial cells and normal infant valvular interstitial cells have the phenotype of activated myofibroblasts, as evidenced by positive staining for vimentin, smooth muscle actin, and metalloproteinase-9. However, the number of mucopolysaccharidosis type I valvular interstitial cells is significantly increased when compared to that of normal cells (P<.0031). Both mucopolysaccharidosis type I (Hurler syndrome) cells and normal valvular interstitial cells express CD34⁺, a hematopoietic and capillary endothelial progenitor cell marker, suggesting a common response to activation.

Conclusions

We conclude that “clear” or “Hurler” cells are valvular interstitial cells with the immunohistochemical phenotype of activated myofibroblasts and may be engaged, albeit ineffectively, in valve repair.

Keywords: Mucopolysaccharide, Valve, Fibroblast