Metformin for the heart
Researchers at the University of Arizona, working under the guidance of Dr. Henk Granzier, in experiments on mice found that metformin, a drug widely used in the treatment of type 2 diabetes mellitus, is effective in the treatment of heart failure with a preserved ejection fraction.
Almost 50% of patients with heart failure have a preserved ejection fraction, that is, the heart has normal contractility, but due to the compaction of the wall of the left ventricle, it cannot completely relax between beats, which reduces its blood filling. The result of this is a deterioration of the blood supply to the entire body, accompanied by shortness of breath and excessive tension during exercise.
Heart failure with a preserved ejection fraction is more common in women, and risk factors for its development include hypertension, old age and obesity. Unlike other forms of the disease, heart failure with a preserved ejection fraction is currently not amenable to pharmacological therapy.
The authors drew attention to the previously demonstrated ability of metformin to enhance dilation (stretching) of the left ventricle and reduce the risk of heart failure in patients with diabetes mellitus and suggested that it may have a positive effect on the condition of patients with heart failure with preserved ejection fraction. Experiments on a mouse model of the disease confirmed the validity of the hypothesis and demonstrated the ability of the drug to reduce the rigidity of the left ventricular wall and improve the ability of animals to exercise.
Upon further study of the issue, it was found that metformin relaxes the left ventricle by increasing the extensibility of the titin cardiac muscle protein. Titin acts as a molecular spring that promotes muscle contraction after stretching. Its extensibility is regulated by the activity of enzymes that attach phosphate groups to the "springy" elements of the protein. In patients with heart failure with a preserved ejection fraction, one of these elements, known as N2B, contains very few phosphate groups, which causes abnormal rigidity of titin. Metformin therapy increases the number of phosphate groups on mouse titin N2B, increasing the extensibility of the protein molecule and, accordingly, reducing the rigidity of the heart muscle.
Based on these observations, the authors concluded that metformin is a potentially effective treatment for heart failure with a preserved ejection fraction. Given that this drug has already been approved for clinical use and is well tolerated by patients, its ability to affect cardiac muscle titin provides a unique opportunity to quickly transfer the experimental approach into clinical practice.
Article by Rebecca E. Slater et al. Metformin improves diastolic function in an HFpEF-like mouse model by increasing titin compliance published in the Journal of General Physiology.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru According to the University of Arizona: UA Scientists Discover Diabetes Drug Could be Used to Treat Common Heart Failure Syndrome.