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Circulating Cardiovascular Proteomic Associations With Genetics and Disease.

Kathryn A McGurk1,2,3, Lara Curran1,2,4, Arunashis Sau1,5

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Angiotensin-converting enzyme 2 (ACE2) shows a protective effect against hypertension and type-2 diabetes. This finding suggests potential therapeutic benefits of ACE2 for cardiovascular disease prevention.

Keywords:
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Area of Science:

  • Proteomics and Cardiovascular Disease Biomarkers
  • Systems Biology and Disease Mechanisms

Background:

  • Circulating proteome analysis offers insights into disease biomarkers and severity.
  • Understanding protein-disease relationships is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate the interplay between cardiovascular disease (CVD) risk factors and protein measures.
  • To explore potential causal links mediated by circulating proteins in CVD development.

Main Methods:

  • Analysis of 9 plasma proteins (e.g., ACE2, BNP, NT-proBNP) in over 45,000 UK Biobank participants.
  • Utilized phenome-wide and genome-wide association studies (GWAS).
  • Employed two-sample Mendelian randomization for causal inference.

Main Results:

  • Circulating protein levels varied significantly with demographic and lifestyle factors (age, sex, alcohol, smoking, medication).
  • GWAS identified genetic variants (near GCKR, APOE, SERPINA1) influencing protein levels (BAG3, CDKN1A, NOTCH1).
  • Angiotensin-converting enzyme 2 (ACE2) demonstrated a protective role against hypertension and type-2 diabetes.

Conclusions:

  • ACE2 is causally protective for hypertension and diabetes, suggesting therapeutic potential.
  • This study enhances understanding of circulating protein pathways in cardiovascular disease dynamics.