University of Pittsburgh researchers have discovered a way to stop calcification using STAT5 inhibitors for the treatment or prevention of cardiovascular calcification. This discovery can replace current options for valve replacements, which develop calcification and fail after approximately 10 years requiring additional surgery, as well as individuals with advanced atherosclerotic plaques, or peripheral artery disease.
Description
Cardiovascular calcification is a complex and dynamic pathology. Calcification in atherosclerotic plaque distorts mechanical load bearing which contributes to plaque rupture, and calcification of the aortic valve incurs a higher risk of stroke and leads to heart failure. Non-atherosclerotic medial arterial calcification in the lower extremity arteries disrupts arterial compliance and is a leading cause of chronic and acute limb ischemia in peripheral artery disease. Currently there is no therapy that can halt or reverse cardiovascular calcification. University of Pittsburgh researchers have discovered that early in osteogenic differentiation of valve interstitial cells and vascular smooth muscle cells, telomerase reverse transcriptase (TERT) interacts with Signal Transducer and Activator of Transcription 5A/B (STAT5) to bind to the promoter of RUNX2. RUNX2 is the master transcription factor required for osteogenesis. Disrupting this interaction is a targeted approach to stall or prevent osteogenic reprogramming of cardiovascular cells and cardiovascular calcification.
Applications
• Individuals with calcific aortic valve disease
• Individuals with detectable levels of coronary artery calcium scores
Advantages
• Novel and more cost-effective approach
• Less invasive than aortic valve replacement
Invention Readiness
Stage of development: Ex vivo studies on human valve tissue
IP Status
https://patents.google.com/patent/WO2023205569A1Related Publication(s)
Small, A. M., Yutzey, K. E., Binstadt, B. A., Voigts Key, K., Bouatia-Naji, N., Milan, D., Aikawa, E., Otto, C. M., & St. Hilaire, C. (2024). Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association. Circulation, 150(6). https://doi.org/10.1161/cir.0000000000001254
Cuevas, R. A., Wong, R., Joolharzadeh, P., Moorhead, W. J., 3rd, Chu, C. C., Callahan, J., 4th, Crane, A., Boufford, C. K., Parise, A. M., Parwal, A., Behzadi, P., & St. Hilaire, C. (2023). Ecto-5′-nucleotidase (Nt5e/CD73)-mediated adenosine signaling attenuates TGFβ-2 induced elastin and cellular contraction. American Journal of Physiology-Cell Physiology, 324(2), C327–C338. https://doi.org/10.1152/ajpcell.00054.2022
Cuevas, R. A., Chu, C. C., Moorhead III, W. J., Wong, R., Sultan, I., & St. Hilaire, C. (2021). Isolation of Human Primary Valve Cells for In vitro Disease Modeling. Journal of Visualized Experiments, 170. https://doi.org/10.3791/62439
