New insight into the role of lipid metabolism-related proteins in rheumatic heart valve disease

Abstract

Purpose: The aim of this study was to determine the expression of lipid metabolism-related proteins in rheumatic heart valve disease (RHVD).

Methods: This retrospective study involved a total of 20 cases of moderate or severe rheumatic mitral valve stenosis and 4 cases of mitral regurgitation due to secondary causes from September 2018 to September 2021. The patients enrolled included 12 males and 12 females who underwent surgical excision of the mitral valve at the cardiac surgery department of Hainan General Hospital. The samples of mitral valve were collected during surgery treatment as the study group, and mitral valves collected from patients with ischemic heart disease were allocated into the control group. Hematoxylin-eosin (HE), oil red staining and immunohistochemical (IHC) staining were conducted to compare the expression of lipid metabolism-related proteins (ATP-binding cassette transporter A1 and acyl-coenzyme A: cholesterol acyltransferase-1), and real-time polymerase chain reaction (RT-PCR) was applied to compare the mRNA levels of ABCA1, ACAT1, and the inflammatory cytokines TNF-α, IL-10, and MCP-1.

Results: In general, the rheumatic mitral valve showed leaflet thickening along with border adhesions and visible yellow fats. Oil red O staining also revealed the abovementioned results as well as fat cells. Both ABCA1 and ACAT1 were expressed in the rheumatic mitral valve via IHC, whereas only ACAT1 showed a faint level of expression in the ischemic mitral valve with no expression of ABCA1. In addition, compared with the ischemic mitral valve, RT-PCT showed increased mRNA expression levels of ABCA1, ACAT1, and the inflammatory cytokines TNF-α, IL-10, and MCP-1 (P < 0.05). After dividing the RMs into two groups for RT-PCR, we found that the higher the expression of ABCA1 and ACAT1 was, the lower the relative expression of inflammatory factors.

Conclusion: This study showed that adipose tissue, adipose cells, and lipid transport-related proteins were expressed strongly in the rheumatic mitral valve, suggesting that adipose tissue formation might be one of the important pathways in the pathology of rheumatic heart disease. In addition, adipose tissue and adipocytes were also involved in the inflammatory process. These data provide new insight into pathological mechanisms in rheumatic heart disease.

Keywords: Hematoxylin–eosin staining; Immunohistochemical staining; Lipid metabolism; Rheumatic mitral valve disease.

Fig. 1

General specimen and HE/oil red staining. A Rheumatic mitral valve shows thickening, adhesions, visible yellow fat and calcification; B HE staining (× 40). Rheumatic valves show peri-fibrous tissue arranged disorderly; C, fat-like cells (× 100); D neovascularization. (× 100); E rheumatic mitral valve oil red staining

Fig. 2

Immunohistochemical staining of CD68. The expression of CD68 was not found in ischemic mitral valve (A, × 40) but was found in rheumatic mitral valve n. (B, × 100)

Fig. 3

Immunohistochemical staining of ABCA1 and ACAC1. The expression of ABCA1 was not found in the ischemic mitral valve (A, × 40). ABCA1 expression and rheumatoid nodules in the rheumatic mitral valve (B, × 40). The expression of ACAT1 was weakly positive in the ischemic mitral valve (C × 40. Increased expression of ACAT1 was found in the rheumatic mitral valve (D, × 40)

Fig. 4

The mRNA expression levels of lipid metabolism-related genes and inflammatory factors