Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies
Abstract Background Studies on the pro-inflammatory effects of primary aldosteronism (PA) in humans have largely relied on measurements of circulating inflammatory biomarkers and are mostly observational in nature, making it difficult to establish a causal relationship between PA and inflammatory re...
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| Language: | English |
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BMC
2025-07-01
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| Series: | Diabetology & Metabolic Syndrome |
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| Online Access: | https://doi.org/10.1186/s13098-025-01875-6 |
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| author | Zhiyu Zhang Yun Du Fei Zhang Xiaoqi Li Lei Rong Heng Zhu Jie Tan Jing Huang |
| author_facet | Zhiyu Zhang Yun Du Fei Zhang Xiaoqi Li Lei Rong Heng Zhu Jie Tan Jing Huang |
| author_sort | Zhiyu Zhang |
| collection | DOAJ |
| description | Abstract Background Studies on the pro-inflammatory effects of primary aldosteronism (PA) in humans have largely relied on measurements of circulating inflammatory biomarkers and are mostly observational in nature, making it difficult to establish a causal relationship between PA and inflammatory responses. In addition, the association between PA and bone mineral density (BMD) remains controversial and warrants further investigation. Objective This study aimed to evaluate the causal effects of PA on circulating inflammatory proteins and bone mineral density. Methods We performed a Mendelian randomization (MR) analysis to assess the causal relationships between PA and 91 circulating inflammatory proteins, as well as BMD at four anatomical sites. The findings were further validated using a rat model and clinical data. Results MR analysis revealed significant inverse causal associations between PA and the circulating levels of interleukin-10 receptor subunit beta (IL-10RB) and hepatocyte growth factor (HGF). These findings were further supported by the rat model results, in which serum IL-10RB (2.10 ± 1.18 ng/mL) and HGF (1120.95 ± 144.33 pg/mL) levels in the Aldo-salt group were significantly lower than those in both the Aldo-salt-Epl group (4.80 ± 1.40 ng/mL and 1434.74 ± 192.45 pg/mL, respectively) and the control group (5.07 ± 0.79 ng/mL and 1540.42 ± 316.32 pg/mL, respectively) (P < 0.05). Consistently, clinical data showed that patients with PA had significantly lower serum IL-10Rb and HGF levels compared to those with essential hypertension (EH) (1146.20 ± 178.23 vs. 1660.49 ± 238.44 pg/mL and 1082.93 ± 231.47 vs. 1935.18 ± 296.44 pg/mL, respectively; P < 0.001 for both). Notably, MR analysis did not identify any significant causal associations between PA and bone mineral density at the total body, forearm, femoral neck, or lumbar spine. Conclusion This study is the first to demonstrate a causal relationship between PA and reduced circulating levels of IL-10RB and HGF, suggesting that PA may promote disease progression by impairing anti-inflammatory defenses and providing new insights for diagnostic and therapeutic strategies targeting inflammation-related pathways. |
| format | Article |
| id | doaj-art-41e76091296c4854908fa4fbe059a46e |
| institution | DOAJ |
| issn | 1758-5996 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-41e76091296c4854908fa4fbe059a46e2025-08-20T03:05:07ZengBMCDiabetology & Metabolic Syndrome1758-59962025-07-0117111510.1186/s13098-025-01875-6Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studiesZhiyu Zhang0Yun Du1Fei Zhang2Xiaoqi Li3Lei Rong4Heng Zhu5Jie Tan6Jing Huang7Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Nephrology, the Second People’s Hospital of Yibin CityDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract Background Studies on the pro-inflammatory effects of primary aldosteronism (PA) in humans have largely relied on measurements of circulating inflammatory biomarkers and are mostly observational in nature, making it difficult to establish a causal relationship between PA and inflammatory responses. In addition, the association between PA and bone mineral density (BMD) remains controversial and warrants further investigation. Objective This study aimed to evaluate the causal effects of PA on circulating inflammatory proteins and bone mineral density. Methods We performed a Mendelian randomization (MR) analysis to assess the causal relationships between PA and 91 circulating inflammatory proteins, as well as BMD at four anatomical sites. The findings were further validated using a rat model and clinical data. Results MR analysis revealed significant inverse causal associations between PA and the circulating levels of interleukin-10 receptor subunit beta (IL-10RB) and hepatocyte growth factor (HGF). These findings were further supported by the rat model results, in which serum IL-10RB (2.10 ± 1.18 ng/mL) and HGF (1120.95 ± 144.33 pg/mL) levels in the Aldo-salt group were significantly lower than those in both the Aldo-salt-Epl group (4.80 ± 1.40 ng/mL and 1434.74 ± 192.45 pg/mL, respectively) and the control group (5.07 ± 0.79 ng/mL and 1540.42 ± 316.32 pg/mL, respectively) (P < 0.05). Consistently, clinical data showed that patients with PA had significantly lower serum IL-10Rb and HGF levels compared to those with essential hypertension (EH) (1146.20 ± 178.23 vs. 1660.49 ± 238.44 pg/mL and 1082.93 ± 231.47 vs. 1935.18 ± 296.44 pg/mL, respectively; P < 0.001 for both). Notably, MR analysis did not identify any significant causal associations between PA and bone mineral density at the total body, forearm, femoral neck, or lumbar spine. Conclusion This study is the first to demonstrate a causal relationship between PA and reduced circulating levels of IL-10RB and HGF, suggesting that PA may promote disease progression by impairing anti-inflammatory defenses and providing new insights for diagnostic and therapeutic strategies targeting inflammation-related pathways.https://doi.org/10.1186/s13098-025-01875-6Primary aldosteronismBone mineral densityBiomarkersMendelian randomization91 circulating inflammatory proteinsInterleukin-10 receptor subunit beta |
| spellingShingle | Zhiyu Zhang Yun Du Fei Zhang Xiaoqi Li Lei Rong Heng Zhu Jie Tan Jing Huang Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies Diabetology & Metabolic Syndrome Primary aldosteronism Bone mineral density Biomarkers Mendelian randomization 91 circulating inflammatory proteins Interleukin-10 receptor subunit beta |
| title | Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies |
| title_full | Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies |
| title_fullStr | Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies |
| title_full_unstemmed | Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies |
| title_short | Causal effects of primary aldosteronism on inflammation and bone density: evidence from Mendelian randomization, animal, and clinical studies |
| title_sort | causal effects of primary aldosteronism on inflammation and bone density evidence from mendelian randomization animal and clinical studies |
| topic | Primary aldosteronism Bone mineral density Biomarkers Mendelian randomization 91 circulating inflammatory proteins Interleukin-10 receptor subunit beta |
| url | https://doi.org/10.1186/s13098-025-01875-6 |
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