Vascular and valve calcification is a very prevalent pathologic deposition of calcium in arterial walls or valve leaflets. The prevalence of vascular calcification is between 31% to 55% in asymptomatic adult population, and increases with age. There is a major unmet need for new therapeutics to specifically treat vascular or valve calcification, since currently no therapeutic solution exists. A pathologic osteochondrogenic differentiation of vascular smooth muscle cells promotes arterial calcifications, a process associated with significant morbidity and mortality. The molecular pathways promoting this pathology are not completely understood. Lab research showed that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process. Gain- and loss-of function assays demonstrate that HDAC4 is a positive regulator driving this pathology. Lab results establish a cytoplasmic role for HDAC4 and identify HDAC4, SIK, and ENIGMA as mediators of vascular calcification. Accordingly, the research group identified potential drug target and developed assays and models to screen and validate small molecular inhibitors for targeting this pathologic condition, ranging from high-throughput ready assays to animal models.
- Specific treatment of vascular and valve calcification
Applications and Opportunities
- Cardiovascular diseases; vascular and valve calcification