SCIENTISTS have uncovered new biological links between blood pressure and cardiovascular disease, identifying specific plasma proteins that appear to play a causal role in raising blood pressure and increasing the risk of heart attacks and strokes.
Unravelling the Molecular Pathways of Blood Pressure Regulation
High blood pressure is a leading cause of cardiovascular disease worldwide, yet the biological processes behind its development are not fully understood. This large-scale genetic study provides a deeper look into the proteomic landscape of blood pressure, exploring how thousands of proteins in the bloodstream influence its regulation and contribute to conditions such as coronary artery disease (CAD) and stroke. By combining genetic and observational data, the research helps clarify how certain proteins mediate cardiovascular risk through their impact on blood pressure, paving the way for new therapeutic targets.
Genetic Insights into Blood Pressure and Heart Risk
The research team conducted a proteome-wide Mendelian randomisation study using genetic data from 2007 plasma proteins to determine their causal effects on blood pressure levels. Of these, 242 proteins showed significant associations with blood pressure, while 48 were also linked to coronary artery disease or stroke. Four proteins (ACOX1, FGF5, FURIN, and MST1) showed particularly strong evidence of shared genetic pathways influencing both blood pressure and cardiovascular outcomes.
FURIN and FGF5 were closely tied to both blood pressure and stroke risk, while ACOX1, FGF5, and MST1 showed potential causal effects on coronary artery disease. Further analysis revealed that between 30.5% and 77.2% of the cardiovascular risk linked to these proteins was mediated through blood pressure regulation. Observational analyses using data from the UK Biobank supported these findings, confirming the biological relevance of these protein pathways in long-term cardiovascular health.
Clinical Implications and Future Directions
These findings emphasise that blood pressure acts as a crucial intermediary between protein activity and cardiovascular risk. Understanding these molecular pathways may enable earlier and more precise identification of individuals at risk of hypertension-related disease. The study also highlights potential new protein targets, such as ACOX1 and FURIN, for future drug development. Integrating genetic and proteomic data into clinical assessment could ultimately enhance the prevention and treatment of cardiovascular conditions driven by elevated blood pressure.
Reference
Meena D et al. Blood pressure, plasma proteins, and cardiovascular diseases: a network Mendelian randomization and observational study. European Heart Journal. 2025:ehaf725.
