1. Thiol-Reactive Compounds Attenuate Aortic Stenosis

2. Background
Aortic stenosis is a degenerative disease characterized by increased fibrosis and narrowing of aortic valves
Aortic stenosis leads to increased valve-wall shear stress
Platelets are a rich source of latent TGF-β1, which can be activated by increased wall shear stress

3. Aortic Stenosis Problem OMRF’s Solution
Aortic stenosis primarily affects people over 65 years of age, and the only treatment available is valve replacement
Inhibiting platelet-derived TGF-β1 activation with Thiol-Reactive Compounds such as, N-Acetyl Cysteine (NAC) and galunisertive (LY ), represents a potential non-invasive therapeutic intervention for aortic stenosis

4. One of the compounds used in proof-of-concept studies was N-Acetyl Cysteine (NAC)
Echocardiographic quantification of stenosis in NAC-treated and NAC-untreated atherosclerotic prone mice at 3-5 and 5-6 months on a high fat diet
Data

5. Summary
Dr. Ahamed has shown that platelet-derived TGF-β1 directly contributes to aortic stenosis progression
Atherosclerotic prone mice LDLR mice lacking platelet- derived TGF-β1 were protected from developing aortic stenosis
Thiol-Reactive compounds, including NAC and galunisertive (LY ), significantly attenuated aortic stenosis progression in LDLR mice by blocking platelet-derived TGF-β1 activation

6. Jasimuddin Ahamed, Ph.D. Assistant Member
Cardiovascular Biology Research Program