Relationship between cathepsins and cardiovascular diseases: a Mendelian randomized study

Area of Science:

• Genetics
• Cardiology
• Biochemistry

Background:

• Cardiovascular diseases (CVDs) are a leading cause of age-related mortality globally.
• Cathepsins, crucial protein-degrading enzymes, are increasingly implicated in CVD pathogenesis.
• The precise causal link between cathepsins and CVDs requires further investigation.

Purpose of the Study:

• To investigate the causal relationships between specific cathepsins and various cardiovascular diseases using Mendelian randomization (MR).

Main Methods:

• Utilized single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study and seven cardiovascular GWAS datasets.
• Employed inverse variance weighted (IVW), weighted median, and MR-Egger methods for robust MR analysis.
• Assessed heterogeneity and performed sensitivity analyses using Cochran's Q test, MR-PRESSO, and leave-one-out methods.

Main Results:

• Cathepsin E significantly increased the risk of myocardial infarction (MI) and ischemic stroke (IS).
• Cathepsin L2 demonstrated a protective effect against chronic heart failure (CHF) and atrial fibrillation (AF).
• Cathepsin O was associated with an elevated risk of IS and AF.

Conclusions:

• Cathepsin E acts as a risk factor for MI and IS.
• Cathepsin L2 exhibits protective effects against CHF and AF.
• Cathepsin O is identified as a risk factor for IS and AF.