Background
Pulmonary embolism manifests with distinct clinical features, resulting from the obstruction of arteries due to the retention of blood clots in the pulmonary artery. This condition exhibits a significant association with cardiovascular diseases. Cathepsin, a protein intricately linked to cardiovascular disorders, plays a crucial role in the degradation of proteins within cells and tissues. Its involvement spans various physiological and pathological processes, including cell signaling, immune responses, tissue repair, and inflammation. Functioning as a protease, cathepsin possesses the ability to cleave protein molecules, influencing protein levels both inside and outside the cell. This regulatory capacity impacts cell function and tissue structure.
Methods
We employed single nucleotide polymorphisms of four cathepsins (cathepsin L1, cathepsin B, and cathepsin D) as instrumental variables, obtained from a comprehensive genome-wide database. Our investigation covered pulmonary embolism. We employed traditional inverse variance weighting (IVW) and other established methods to assess causality while conducting tests for heterogeneity and sensitivity. Furthermore, we conducted a reverse causality analysis using Mendelian randomization (MR) to explore the inverse relationship between exposure factors and the outcomes.
Results
The IVW analysis demonstrated that cathepsin L1 was associated with pulmonary embolism with an odds ratio (OR) of 1.179 (95% CI, 1.017-1.367) and a P-value of 0.0028, cathepsin B ,as evidenced by an odds ratio (OR) of 0.972 (95% CI, 0.871-1.084) with a P-value of 0.61 (>0.05), and cathepsin D as indicated by an odds ratio (OR) of 0.990 (95% CI, 0.815-1.202) with a P-value of 0.922 (>0.05), leading to an increased risk in these conditions. Furthermore, there was no correlation found between cathepsin D、cathepsin B and pulmonary embolism.
Conclusions
Our study marks the pioneering application of Mendelian randomization to authenticate the causal links between three cathepsins and the susceptibility to pulmonary embolism. The results indicate a noteworthy protective effect of cathepsin L1 against the risk of pulmonary embolism, positioning it as a promising new biological target for addressing this condition. Importantly, no causal relationship was discerned between cathepsin B and cathepsin D and pulmonary embolism. These findings hold the potential to offer valuable clinical insights and recommendations, shaping the landscape for the development of novel treatments for pulmonary embolic disease.