A study conducted by researchers at the MRC Laboratory of Medical Sciences (LMS) and Imperial College London has found that the protein ACE2 may have a protective role against high blood pressure and type 2 diabetes. These two conditions are widespread, affecting millions globally.
The research, published in Circulation: Genomic and Precision Medicine, was led by Dr Kathryn McGurk from the Computational Cardiac Imaging group and the Cardiovascular Genomics Precision Medicine group at LMS. The team analyzed nine key proteins in more than 45,000 blood samples from the UK Biobank. Among these proteins were ACE2, BNP, NT-proBNP, and troponin I—all known to be involved in heart function and disease.
The study found significant differences in circulating protein levels based on factors such as age, sex, ancestry, genetics, lifestyle, and medication use. Notably, higher levels of ACE2 were observed in individuals diagnosed with high blood pressure or diabetes. This effect was especially pronounced among females and was influenced by genetic changes associated with diabetes.
Using a method called two-sample Mendelian randomisation for genetic analysis, researchers found evidence suggesting that increased ACE2 levels may serve as a protective response against high blood pressure and type 2 diabetes.
ACE2 became widely recognized during the COVID-19 pandemic because it is the protein that allows the virus to enter human cells. It breaks down angiotensin II—a compound that tightens blood vessels—and produces substances that relax them. Therefore, elevated ACE2 levels seen in people with high blood pressure might help counteract vessel constriction.
The identification of ACE2 as a potential biomarker could impact patient care due to its apparent protective effects within the cardiovascular system. "This work highlights how discovery data science can find novel disease biomarkers and therapies, as well as shift our understanding of current therapies and which patients can benefit most," said Dr Kathryn McGurk. "The key to this work is interdisciplinary collaboration: with our enthusiastic early career colleagues (Dr Lara Curran, Dr Arun Sau), encouragement and input from more senior colleagues (Prof Declan O'Regan, Prof James Ware, Prof Fu Siong Ng), and important clinical insights (Dr Brian Halliday)."
Currently prescribed drugs for high blood pressure—ACE inhibitors—work by blocking another protein called ACE1 which produces angiotensin II. The findings suggest that balancing ACE1 and ACE2 could influence how effective these medications are for individual patients. People with naturally different levels of ACE2 might respond better to certain treatments; this insight could lead to more personalized approaches based on measuring blood ACE2 levels.
Future studies will examine whether increasing or mimicking ACE2 activity could improve treatment outcomes for those with high blood pressure or diabetes. Previous preclinical research has shown that metformin—a common anti-diabetic drug—increases expression of ACE2 as part of its action.
This research received primary support from organizations including the British Heart Foundation, Medical Research Council, National Institute for Health Research Imperial College Biomedical Research Center, Sir Jules Thorn Charitable Trust, and Rosetrees Trust.
Kathryn McGurk is a British Heart Foundation Immediate Research Fellow at LMS and Imperial's National Heart and Lung Institute.
