Cardiovascular

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

Isaza S, Hernández-García M, et al. • Molecular biomedicine • 2026

PubMed 42957922 DOI 10.1186/s43556-026-00609-y
TL;DR

BMP12 is identified as a previously unrecognized mediator of vascular remodeling that promotes pro-atherogenic effects in VSMCs through canonical BMP signaling, and elevated circulating BMP12 is associated with subclinical vascular damage, supporting its potential as a novel candidate biomarker for CV risk.

Key Findings

Results

BMP12 treatment increased migration and calcification of vascular smooth muscle cells (VSMCs) in vitro.

  • The experimental study evaluated BMP12 effects on atherogenesis-related processes in VSMCs.
  • The abstract reports 'increased migration and calcification in BMP12-treated VSMCs'.
  • Specific effect sizes and p-values are not given in the abstract.
Results

BMP12 induced osteogenic markers and migration-related genes while reducing the contractile marker Desmin in VSMCs.

  • BMP12 increased expression of osteogenic markers RUNX2 and ALP.
  • BMP12 increased expression of the migration-related gene Mmp9.
  • BMP12 reduced expression of the contractile marker Desmin, consistent with a phenotypic switch.
Results

The pro-atherogenic effects of BMP12 in VSMCs were blocked by BMP type I receptor inhibitors, indicating involvement of canonical BMP signaling.

  • The inhibitors used were DMH2 and LDN-193189.
  • The authors conclude BMP12 acts 'through canonical BMP signaling'.
Results

Serum BMP12 levels were higher in patients with cardiovascular disease and type 2 diabetes.

  • Circulating BMP12 was measured in a well-characterized cohort of patients with CV risk factors.
  • Levels were correlated with cardiometabolic disorders and vascular damage markers.
  • Cohort size and numerical values are not given in the abstract.
Results

Circulating BMP12 was elevated in patients with carotid and femoral plaques and correlated with plaque volume.

  • Elevated levels were seen in patients with plaques at both carotid and femoral sites.
  • BMP12 concentrations correlated with plaque volume.
  • This supports an association with subclinical vascular damage.
Results

BMP12 emerged as an independent predictor of femoral atherosclerosis.

  • The abstract states BMP12 was an independent predictor of femoral atherosclerosis.
  • Odds ratios, confidence intervals and covariates are not provided in the abstract.
Conclusions

The authors conclude BMP12 is a previously unrecognized mediator of vascular remodeling and a candidate biomarker for CV risk.

  • The rationale was BMP12's structural and signaling similarity to BMP2, which promotes osteogenic switching and pro-atherogenic responses in VSMCs.
  • Combined in vitro and clinical data support BMP12 as a contributor to atherosclerosis progression.

What This Means

This study asked whether a protein called BMP12, which is related to a protein known to drive harmful changes in blood vessel walls, might also contribute to atherosclerosis (hardening and plaque buildup in arteries). In lab experiments on vascular smooth muscle cells, BMP12 made the cells move more and calcify more, switched on bone-forming genes (RUNX2, ALP) and a migration-related gene (Mmp9), and lowered a marker of normal muscle-cell function (Desmin). Drugs that block BMP receptors (DMH2 and LDN-193189) prevented these effects. In a clinical part of the study, patients with cardiovascular disease and type 2 diabetes had higher blood levels of BMP12. Levels were also higher in people with plaques in the carotid (neck) and femoral (leg) arteries, and they tracked with plaque volume. BMP12 was an independent predictor of plaque in the femoral arteries. This research suggests BMP12 may help drive vascular damage and could one day serve as a blood marker of cardiovascular risk or a treatment target. However, the abstract does not give cohort sizes or effect sizes, and the clinical findings show associations rather than proof of cause, so further research would be needed to confirm these results.

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Citation

Isaza S, Hernández-García M, Fernández-García C, Pérez-Utrera C, Álvarez-Rubal M, Muñoz J, et al.. (2026). Bone morphogenetic protein 12: a novel target for cardiovascular disease.. Molecular biomedicine. https://doi.org/10.1186/s43556-026-00609-y