Apolipoprotein C-1 Induced Apoptosis
Apolipoprotein C-I, a small basic protein in human blood, induces apoptosis in cultured human arterial smooth muscle cells through the neutral sphingomyelin (N-SMase) pathway, and the subsequent second messenger steps. An inhibitor of N-SMase abrogates this effect. Description (Set) Proposed Use (Set) Eighty % of heart attacks occur through the rupture of an unstable plaque that usually occludes only 20- 40 % of the coronary artery. The class of drugs called the statins stabilizes such an unstable plaque by decreasing the cholesterol burden to the inflamed macrophages, yet this class only prevents 30 % of heart attacks. If apoC-I promotes apoptosis (or cell death) of the arterial smooth muscle cells in the cap of the plaque, this will promote an unstable plaque, which can rupture causing heart attack and/or sudden death. The drug target is an inhibitor of N-SMase that will prevent the effect of apoC-I on apoptosis in these cells, leading to greater stabilization of the plaque. Alternatively, one can develop a drug part of which has a structure similar to apoC-I, also preventing the apoC-I from interacting with N-SMase, and stabilizing the plaque.
Chatterjee, Subroto B.
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