The University of Pittsburgh
The group of Prof. Dr. Guy Salama from the University of Pittsburgh, Department of Medicine, Heart and Vascular Institute and Relaxera are investigating the effects of relaxin-2 on myocyte stiffness by altering the structural protein titin in an animal model.
Cardiovascular diseases are the number 1 cause of death globally. CVDs include disorders of the heart and blood vessels, coronary heart disease, cerebrovascular disease, heart failure, and others. About 50% of patients with heart failure suffer from HFpEF, heart failure with preserved ejection fraction. Increased cardiomyocyte passive stiffness is part of the pathophysiology. This stiffness is largely due to modifications of cardiac titin.
Titin is the largest known protein consisting of more than 34,000 amino acids in humans and plays a major role for muscle contraction and relaxation. The cardio-specific titin N2B shows hypophosphorylation in HFpEF.
Can relaxin modify the expression levels of the dominant isoforms of titin (N2BA and N2B) or the phosphorylation status? Former studies (also in humans) have shown that relaxin-2 has anti-fibrotic effects on multiple organs including the heart, and its signalling via protein kinases A and G may well target titin phosphorylation status.
The relaxin effect will be measured by (amongst others) histological examinations on myocardial fibrosis, by skinned fibre experiments, biochemical examination of titin expression and phosphorylation, and by echo examinations with assessment of diastolic function. Inflammation markers will be examined as well.
This study could further establish relaxin-2 treatment as a potential therapy for HFpEF, until now the greatest unmet medical need in contemporary cardiology .