Abstract 13401: Prothymosin Alpha (Protα) Associates With Pathogenesis and Sex Predisposition in Rheumatic Heart Valve Disease

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-11, Vol.142 (Suppl_3 Suppl 3), p.A13401-A13401
• Main Authors: Passos, Livia, Blaser, Mark C, Romero, Dayanna, Becker Greene, Dakota, Lupieri, Adrien, Sukhova, Galina K, Dal-bianco, Jacob P, Libby, Peter, Singh, Sasha A, Aikawa, Masanori, Levine, Robert A, Nunes, Maria Do Carmo P, Aikawa, Elena
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.13401

IntroductionAcute rheumatic fever (ARF) results from autoimmune responses to group A streptococcus. ARF can cause chronic rheumatic heart valve disease (RHVD), a major public health burden in low- and middle-income countries. Although ARF affects both sexes equally, females have a higher prevalence of RHVD. We identified a target protein, ProTα, that may contribute to pathophysiology of and gender predisposition in RHVD. Estradiol regulates ProTα, which influences transcriptional activity of the estrogen receptor (ER). MethodsHuman heart valves (n=120) obtained from heart transplantation and valve replacement surgeries, including non-diseased mitral and aortic valves (NDMV and NDAV, n=17/group), rheumatic mitral and aortic valves (RMVD, n=45; RAVD, n=8) and calcifying valves from patients with calcific aortic valve disease (CAVD, n=33) underwent proteomic and network analyses, and immunohistochemical assessment of CD68, CD4, CD8 and ProTα. ProTα levels were measured in plasma and peripheral mononuclear cells (PBMCs) from RHVD patients and healthy donors (n=14/group) by ELISA and flow cytometry. ResultsA comparison of proteomes from NDMV and NDAV established the baseline differences between valve types. 12 proteins were enriched (q