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

Abstract

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.

Differential Immune Response to Bioprosthetic Heart Valve Tissues in the α1,3Galactosyltransferase-Knockout Mouse Model

“…In our study, the strong cellular immune response against human pericardium was observed in the absence of an induced anti-carbohydrate antibody response as determined by our assay with PAEC. This is consistent with the direct activation of macrophages, lymphocytes, and platelets by glutaraldehyde tissue fixation [35].…”

“…Notably, macrophages and lymphocytes have also been observed in BHV retrieved from patients [34,35]. The mechanisms responsible for the immune infiltrates in SVD are not fully understood, but various pathways have been proposed, including the release of proteolytic enzymes and reactive oxygen species [12][13][14][15]35,36]. In the present study, the samples that displayed a prominent and penetrating cellular immune infiltrate were associated with more severe structural alterations.…”

“…The macroscopic examination did not provide much information, but the histological analysis revealed the presence of macrophages, lymphocytes, and plasma cells surrounding the grafted tissue at this time point. Notably, macrophages and lymphocytes have also been observed in BHV retrieved from patients [34,35]. The mechanisms responsible for the immune infiltrates in SVD are not fully understood, but various pathways have been proposed, including the release of proteolytic enzymes and reactive oxygen species [12][13][14][15]35,36].…”

Fibrin deposition on bovine pericardium tissue used for bioprosthetic heart valve drives its calcification

“…Recently, we described that glutaraldehyde-treated bovine pericardium inside a bioprosthetic artificial heart was quickly recovered by fibrin and newly formed endothelial cells ( 6 , 7 ). Although explanted BHVs are infiltrated by inflammatory cells but also fibrotic and endothelial cells ( 8 , 9 ), their involvement in SVD is always a question of debate.…”