Is cell regeneration and infiltration a double edged sword for porcine aortic valve deterioration? A large cohort of histopathological analysis

Background and objective Bioprostheses are the most common prostheses used for valve replacement in the Western medicine. The major flaw of bioprostheses is the occurrence of structural valve deterioration (SVD). This study aimed to assess the pathological features of porcine aortic valve (PAV)-SVD based on histomorphological and immunopathological characteristics of a large cohort of patients. Methods Histopathological data of 109 cases with resected PAV were collected. The type and amount of infiltrated cells were evaluated in the different types of bioprosthetic SVD by immunohistochemical staining. Results The most common cause of SVD was calcification, leaflet tear, and dehiscence (23.9%, 19.3%, and 18.3%, respectively). Immunohistochemical staining demonstrated that macrophages were infiltrated in the calcified, lacerated and dehiscence PAV, in which both M1 and M2 macrophages were existed in the calcified PAV. Importantly, the higher content of M1 macrophages and less content of M2 macrophages were found in the lacerated and dehiscence PAV, and MMP-1 expression was mainly found in the lacerated PAV. The endothelialization rate of leaflet dehiscence was higher than that of calcified and lacerated leaflets. A large number of CD31+/CD11b+ cells was aggregated in the spongy layer in the lacerated and dehiscence PAV. Conclusion Cell regeneration and infiltration is a double edged sword for the PAV deterioration. Macrophage infiltration is involved in the different types of SVD, while only MMP-1 expression is involved in lacerated leaflets. The macrophage subtype of circulating angiogenic cells in dehiscence and tear PAV could be identified, which could reserve macrophages in the PAV-SVD.