Sex-Specific Protein Expression of RAAS-Inhibiting Enzyme RENBP in Cardiomyopathy Patients

All articles of this category (opens in new window) Background: Patient-specific therapy is of utmost importance in modern medicine, particularly regarding cardiac diseases and their treatment. The fact that women have been underrepresented in medical studies—starting with excluding female rodents from basic science—hampers patient-specific care. To close this knowledge gap between male and female patients, this study investigated sex-specific differences in cardiac proteomes. We focused on the renin-binding enzyme RENBP, which plays an essential role in inhibiting the renin-angiotensin-aldosterone system (RAAS), controlling blood pressure, and is therefore especially interesting in the context of cardiac diseases. Methods: Utilizing a label-free, in-depth proteomic dataset comprising left and right ventricular samples from 136 (40 female and 96 male) patients with ischemic or dilated cardiomyopathy undergoing in-house heart transplantation, sex-specific protein expression levels were assessed and compared. Results: Cardiac proteomes of 189 left or right ventricles displayed expression of RENBP. A significant difference regarding female (♀) vs. male (♂) expression of RENBP was found (mean ± SD: ♀13.3 ± 0.9; n = 54 vs. ♂12.9 ± 1.2; n = 135; p = 0.007). Comparing this sex-dimorphism in ICM vs. DCM patients showed no significant difference for ICM, whereas in DCM patients the RENBP expression was shown to be significantly different (mean ± SD: ♀13.5 ± 0.6; n = 28 vs. ♂13.1 ± 0.9; n = 56; p = 0.017). In patients with additional comorbidities like diabetes, hyperlipidemia and hypertension the distinction in RENBP expression between female and male was even more significant: diabetes (mean ± SD: ♀13.6 ± 0.6; n = 14 vs. ♂12.6 ± 0.9; n = 30; p = 0.0002); hyperlipidemia (♀13.5 ± 0.6; n = 19 vs. ♂12.8 ± 1.4; n = 70; p = 0.0011); hypertension (♀13.5 ± 0.5; n = 36 vs. ♂13.0 ± 1.2; n = 92; p = 0.0028). Conclusion: These findings suggest a sex-specific differential expression of RENBP in patients with cardiac diseases. The said difference appears to be amplified by comorbidities (diabetes, hyperlipidemia, and hypertension). To explain the effect of comorbidities on expression levels, further research is needed. Considering RENBPs' role in inhibiting the RAAS system, they could be of a more protective nature in cardiac diseases. If confirmed to be upregulated in cardiac diseases, RENBP may be a new therapeutic target—especially for women—allowing for more patient-specific care. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany