Combinatorial Effect of Tyrosine Kinase and Calpain Inhibitors on Human Platelets
Lin, Li.
2017
-
Abstract: Platelets play a major role in the genesis, progression, morbidity,
and mortality of cardiovascular disease (CVD). As CVD progresses, fibrous plaques form
along the arterial walls that become progressively unstable. Sudden plaque rupture induces
and contributes to the development of both thrombosis and coagulation cascade resulting in
lesions such as acute myocardial infarction and/o... read morer ischemic strokes. Platelet glycoprotein
GPIIb/IIIa, also known as integrin αIIbβ3, plays an important role in mediating two
critical platelet processes: platelet activation and clot retraction. A diverse array of
proteins are involved in GPIIb/IIIa signaling. In this study, I investigated the
synergistic role of Src/Syk tyrosine kinases and calpain cysteine proteases in regulating
key platelet signaling cascades. By utilizing specific tyrosine kinase and calpain
inhibitors, we interrogated multiple signaling pathways including platelet adhesion,
spreading, and aggregation. Our results revealed a dual role of both Src/Syk and calpain
signaling pathways in platelet activation, and additive effects of the combination of
pharmacological inhibitors suggest a potential treatment modality for preventing
pathological thrombosis.
Thesis (M.S.)--Tufts University, 2017.
Submitted to the Dept. of Pharmacology & Experimental Therapeutics.
Advisors: Athar Chishti, and Andrew Bohm.
Keyword: Pharmacology.read less - ID:
- xk81jz10v
- Component ID:
- tufts:22755
- To Cite:
- DCA Citation Guide EndNote
