Evidence of Osteogenic Regulation in Calcific Porcine Aortic Valves

  • Fanglin Lu Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Hao Wu Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Yifan Bai Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Dejun Gong Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Cuiping Xia Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Qin Li Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Fanglin Lu Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  • Zhiyun Xu Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China

Abstract

Background: Chemically cross-linked animal tissues, such as porcine aortic valves (PAVs) have many documented advantages over mechanical valves. However, calcification is the major underlying pathologic process that results in bioprosthetic valve failure. Recently, several reports described the expression of noncollagenous bone matrix proteins in bioprosthetic valves and suggested an actively regulated process of tissue repair.

Methods: Thirty-one explanted PAVs with evidence of calcification were collected and examined for the protein expression implicated in myofibroblast activation, osteoblast differentiation, and bone matrix deposition by using immunohistochemistry.

Results: The mean duration that PAVs were implanted was 11.5 ± 5.6 years, ranging from 12 months to 28 years. Pearson correlation analysis showed a significant relationship between the duration and valvular calcification (r = 0.3818,
P = .034). The number of vimentin-positive mesenchymal cells in explanted PAVs was significantly lower than that of unused PAVs (P < .01). However, increased expression of α-smooth muscle actin (α-SMA) (P < .01), proliferating cell nuclear antigen (PCNA, P < .01), Cbfa1/Runx2 (P < .01), osterix (P = .0126), bone sialoprotein (BSP, P < .01), osteocalcin (P < .01), and osteopontin (P < .01) was found in explanted PAVs. Immunohistochemical staining of alkaline phosphatase (ALP) and osteocalcin was negative in the unused PAVs. In explanted PAVs, the expression level of these 2 proteins was also significantly increased.

Conclusions: Our results support the view that PAV calcification is an actively regulated process with osteogenic signaling activation.

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Published
2018-09-13
Section
Articles