**Author details**

Another interesting hypothesis rises from the observation of the double nature of the macro‐ phage cell. In effect, a phenotype committed to tissue regeneration has been discovered besides the typical protective tasks played by these cells. For the similarity to T2 helper lymphocytes, these macrophages have been named M2 and can be characterized by the expression of interleukin-10 (IL-10) and mannose receptor (MR) [261]. In the analysed valve specimens, the immunodetection of CD68, a broad macrophage marker, is associated to the expression of MR

**Figure 4.** Evaluation of M2 macrophages in the mitral valve leaflet of a 26 year-old donor allograft. MR and IL-10 are

This expression pattern of M2 macrophage typical markers is also preserved interspecies in mammals, further corroborating the notion of an evolutionarily conserved, constantly undergoing protection/regeneration process in the heart valve tissue. Porcine, bovine, sheep and non-human primate heart valves share, in fact, a similar cell distribution and localisation

**Figure 5.** M2 macrophage pattern in the aortic valve leaflet of a Macaca fascicularis subject. Magnification: 50x

construct scaffold has been completely replaced by an autologous matrix [262].

As further supportive remark, the extensive identification of stem cells with diverse lineages in heart valves evidences the unique regenerative properties endowed by these tissues [260].

Type 2 macrophages have been additionally found in the early post-implantation phases of bioengineered valve replacements and reported to remain in the implanted tissues until the

likely to be expressed by the same CD68-positive cells. Magnification: 100x

of CD68, MR and IL-10 markers (Figure 5).

and IL-10, as visible in Figure 4.

278 Calcific Aortic Valve Disease

Laura Iop\* and Gino Gerosa

\*Address all correspondence to: laura.iop@unipd.it

Department of Cardiac, Thoracic and Vascular Sciences School of Medicine, University of Padua, Padua, Italy
