title: Lipid-mediated inflammation and degeneration of bioprosthetic heart valves.
abstract: BACKGROUND
  The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs.
  
  
  METHODS
  Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM).
  
  
  RESULTS
  The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets.
  
  
  CONCLUSIONS
  These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.
authors.affiliation: Laval University, Quebec, QC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Shetty
authors.forename: P
authors.initials: P
authors.lastname: Pibarot
authors.forename: A
authors.initials: A
authors.lastname: Audet
authors.forename: R
authors.initials: R
authors.lastname: Janvier
authors.forename: F
authors.initials: F
authors.lastname: Dagenais
authors.forename: J
authors.initials: J
authors.lastname: Perron
authors.forename: C
authors.initials: C
authors.lastname: Couture
authors.forename: P
authors.initials: P
authors.lastname: Voisine
authors.forename: J P
authors.initials: JP
authors.lastname: Després
authors.forename: P
authors.initials: P
authors.lastname: Mathieu
mesh_terms: D000328:Adult; D000368:Aged; D001024:Aortic Valve Stenosis / Q000473:pathology* / Q000517:prevention & control; D001705:Bioprosthesis / Q000009:adverse effects; D002114:Calcinosis / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011183:Postoperative Complications / Q000473:pathology* / Q000517:prevention & control; D011475:Prosthesis Failure; D012307:Risk Factors
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D020780:Matrix Metalloproteinase 9