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Peer-reviewedCC BYMolecular biomedicine

Bone morphogenetic protein 12: a novel target for cardiovascular disease.

  • Stephania C Isaza1
  • Miguel Á Hernández-García1
  • Carlos Ernesto Fernández-García2
  • Carolina Pérez-Utrera3
  • María Álvarez-Rubal1
  • José M Muñoz4
  • Alfonsa Friera4
  • Carmelo García-Monzón1
  • Almudena Gómez-Hernández5
  • Pedro Landete6,7,8
  • Javier Egea1
  • Fernando Alfonso7,9,10
1 more authors
  • Águeda González-Rodríguez11,12
12 affiliations
  1. 1Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Princesa IIS-IP, Madrid, Spain.
  2. 2Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Princesa IIS-IP, Madrid, Spain. [email protected].
  3. 3Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
  4. 4Servicio de Radiodiagnóstico, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria-Princesa IIS-IP, Madrid, Spain.
  5. 5Laboratorio de Enfermedades Hepáticas y Vasculares, Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
  6. 6Servicio de Neumología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria-Princesa IIS-IP, Madrid, Spain.
  7. 7Universidad Autónoma de Madrid, Madrid, Spain.
  8. 8Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
  9. 9Servicio de Cardiología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria-Princesa IIS-IP, Madrid, Spain.
  10. 10Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
  11. 11Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain. [email protected].
  12. 12Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain. [email protected].
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Abstract

Bone morphogenetic protein 12 (BMP12) is known to regulate mesenchymal differentiation and extracellular matrix remodeling. Given its structural and signaling similarities to BMP2, which promotes osteogenic phenotypic switching and pro-atherogenic responses in vascular smooth muscle cells (VSMCs), BMP12 may also contribute to vascular remodeling and atherosclerosis progression. This translational study aimed to unravel BMP12 involvement in cardiovascular disease (CVD). BMP12 effects on atherogenesis-related processes in VSMCs in absence or presence of BMP type I receptor inhibitors (DMH2 and LDN-193189) were evaluated. Additionally, circulating BMP12 levels were measured in a well-characterized cohort of patients with CV risk factors and correlated with cardiometabolic disorders and vascular damage markers. Results from the experimental study showed increased migration and calcification in BMP12-treated VSMCs. Mechanistically, BMP12 induced expression of osteogenic markers (RUNX2 and ALP) and genes related to cellular migration (Mmp9), while reducing contractile marker Desmin. These pro-atherogenic effects were blocked using BMP type I receptor inhibitors. Furthermore, the clinical study revealed higher serum BMP12 levels in patients with CVD and type 2 diabetes. Moreover, circulating BMP12 concentrations were elevated in patients with carotid and femoral plaques, correlating with plaque volume. Notably, BMP12 emerged as an independent predictor of femoral atherosclerosis. Collectively, these findings identify BMP12 as a previously unrecognized mediator of vascular remodeling, promoting pro-atherogenic effects in VSMCs through canonical BMP signaling. The association between elevated circulating BMP12 levels and subclinical vascular damage further supports its potential value as a contributor to atherosclerosis progression and as a promising novel candidate biomarker for CV risk.

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Cite

BibTeXRIS
BibTeX
@article{isaza2026bone,
  title = {{Bone morphogenetic protein 12: a novel target for cardiovascular disease.}},
  author = {Stephania C Isaza and Miguel Á Hernández-García and Carlos Ernesto Fernández-García and Carolina Pérez-Utrera and María Álvarez-Rubal and José M Muñoz and Alfonsa Friera and Carmelo García-Monzón and Almudena Gómez-Hernández and Pedro Landete and Javier Egea and Fernando Alfonso and Águeda González-Rodríguez},
  journal = {Molecular biomedicine},
  year = {2026},
  month = oct,
  doi = {10.1186/s43556-026-00609-y},
  url = {https://europepmc.org/article/MED/42957922},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Bone morphogenetic protein 12: a novel target for cardiovascular disease.
AU  - Stephania C Isaza
AU  - Miguel Á Hernández-García
AU  - Carlos Ernesto Fernández-García
AU  - Carolina Pérez-Utrera
AU  - María Álvarez-Rubal
AU  - José M Muñoz
AU  - Alfonsa Friera
AU  - Carmelo García-Monzón
AU  - Almudena Gómez-Hernández
AU  - Pedro Landete
AU  - Javier Egea
AU  - Fernando Alfonso
AU  - Águeda González-Rodríguez
PY  - 2026
DA  - 2026/10/29
JO  - Molecular biomedicine
DO  - 10.1186/s43556-026-00609-y
UR  - https://europepmc.org/article/MED/42957922
AB  - Bone morphogenetic protein 12 (BMP12) is known to regulate mesenchymal differentiation and extracellular matrix remodeling. Given its structural and signaling similarities to BMP2, which promotes osteogenic phenotypic switching and pro-atherogenic responses in vascular smooth muscle cells (VSMCs), BMP12 may also contribute to vascular remodeling and atherosclerosis progression. This translational study aimed to unravel BMP12 involvement in cardiovascular disease (CVD). BMP12 effects on atherogenesis-related processes in VSMCs in absence or presence of BMP type I receptor inhibitors (DMH2 and LDN-193189) were evaluated. Additionally, circulating BMP12 levels were measured in a well-characterized cohort of patients with CV risk factors and correlated with cardiometabolic disorders and vascular damage markers. Results from the experimental study showed increased migration and calcification in BMP12-treated VSMCs. Mechanistically, BMP12 induced expression of osteogenic markers (RUNX2 and ALP) and genes related to cellular migration (Mmp9), while reducing contractile marker Desmin. These pro-atherogenic effects were blocked using BMP type I receptor inhibitors. Furthermore, the clinical study revealed higher serum BMP12 levels in patients with CVD and type 2 diabetes. Moreover, circulating BMP12 concentrations were elevated in patients with carotid and femoral plaques, correlating with plaque volume. Notably, BMP12 emerged as an independent predictor of femoral atherosclerosis. Collectively, these findings identify BMP12 as a previously unrecognized mediator of vascular remodeling, promoting pro-atherogenic effects in VSMCs through canonical BMP signaling. The association between elevated circulating BMP12 levels and subclinical vascular damage further supports its potential value as a contributor to atherosclerosis progression and as a promising novel candidate biomarker for CV risk.
SN  - 2662-8651
ER  -