Methods of inhibiting smooth muscle cell migration and proliferation
View Patent ↗In particular embodiments, the present invention provides methods of inhibiting smooth muscle cell responses and methods of treating or preventing vascular proliferative disease caused by smooth muscle cell migration and proliferation. More specifically, smooth muscle cell responses are inhibited by introducing an agent into smooth muscle cells, wherein the agent inhibits an activity of one or more members of the myristoylated alanine-rich C kinase substrate (MARCKS) family of proteins. The invention also provides methods of inhibiting expression of one or more genes encoding a member of the MARCKS family of proteins in a cell.
1. A method of inhibiting at least one vascular smooth muscle cell response selected from the group consisting of cell proliferation and cell migration, the method comprising transfecting vascular smooth muscle cells with a nucleic acid molecule that comprises a nucleotide sequence that is at least 90% homologous to a portion of SEQ ID NO: 3, wherein said nucleic acid molecule hybridizes to SEQ ID NO: 3 and inhibits expression of a myristolated alanine-rich C kinase substrate (MARCKS) protein having the amino acid sequence of SEQ ID NO: 4 in said cells, wherein the nucleic acid molecule is about 17 nucleotides to about 29 nucleotides in length.
2. The method of claim 1 , wherein the smooth muscle cell response is cell proliferation.
3. The method of claim 1 , wherein the smooth muscle cell response is cell migration.
4. The method of claim 1 , wherein the nucleic acid molecule induces post-transcriptional silencing of at least one gene encoding the MARCKS.
5. The method of claim 1 , wherein the nucleic acid molecule comprises RNA.
6. The method of claim 5 , wherein the RNA is small interfering RNA (siRNA).
7. The method of claim 1 , wherein the vascular smooth muscle cells are present in a vein graft.
8. The method of claim 1 , wherein the vascular smooth muscle cells are human vascular smooth muscle cells.
9. The method of claim 5 , wherein the RNA is double-stranded.
10. A method of inhibiting expression of one or more genes encoding a MARCKS protein having the amino acid sequence of SEQ ID NO: 4 in a vascular smooth muscle cell, the method comprising transfecting said vascular smooth muscle cell with a nucleic acid molecule that comprises a nucleotide sequence that is at least 90% homologous to a portion of SEQ ID NO: 3, wherein said nucleic acid molecule hybridizes to SEQ ID NO: 3 and induces post-transcriptional silencing of said one or more genes, wherein the nucleic acid molecule is about 17 nucleotides to about 29 nucleotides in length.
11. The method of claim 10 , wherein the nucleic acid molecule comprises RNA.
12. The method of claim 11 , wherein the RNA is double-stranded.
13. The method of claim 11 , wherein the RNA is small interfering RNA (siRNA).
14. The method of claim 10 , wherein the vascular smooth muscle cell is present in a vein graft.
15. The method of claim 10 , wherein the vascular smooth muscle cell is a mammalian vascular smooth muscle cell.
16. The method of claim 15 , wherein the vascular smooth muscle cell is a human vascular smooth muscle cell.
17. The method of claim 1 , wherein the nucleic acid molecule comprises a nucleotide sequence that is 100% homologous to a portion of SEQ ID NO:3.
18. The method of claim 10 , wherein the nucleic acid molecule comprises a nucleotide sequence that is 100% homologous to a portion of SEQ ID NO:3.