Apolipoprotein A-I mimics
Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.
1. A method for treating dyslipidemia, comprising:
administering to a mammal in need thereof a peptide/lipid complex in an amount effective to treat the dyslipidemia, wherein the peptide has the sequence of SEQ ID NO: 108, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the lipid comprises a phospholipid.
3. The method of claim 2 , wherein the phospholipid is sphingomyelin, a (C 1 -C 6 ) alkyl chain phospholipid, phosphatidylcholine (PC), egg phosphatidylcholine, soybean phosphatidylcholine, dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, 1-myristoyl-2-palmitoylphosphatidylcholine, 1-palmitoyl-2-myristoylphosphatidylcholine, 1-palmitoyl-2-stearoylphosphatidylcholine, 1-stearoyl-2-palmitoylphosphatidylcholine, 1-palmitoyl-2-oleoylphosphatidylcholine, 1-oleoyl-2-palmitoylphosphatidylcholine, dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine, dilauroylphosphatidylglycerol, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, a sphingolipid, phosphatidylglycerol, diphosphatidylglycerol, dimyristoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol (DPPG), distearoylphosphatidylglycerol, dioleoylphosphatidylglycerol, dimyristoylphosphatidic acid, dipalmitoylphosphatidic acid, dimyristoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylserine, dipalmitoylphosphatidylserine, brain phosphatidylserine, sphingomyelin, brain sphingomyelin, dipalmitoylsphingomyelin, distearoylsphingomyelin, phosphatidic acid, galactocerebroside, a ganglioside, a cerebroside, dilaurylphosphatidylcholine, (1,3)-D-mannosyl-(1,3)diglyceride, aminophenylglycoside, a 3-cholesteryl-6′-(glycosylthio)hexyl ether glycolipid, cholesterol, or a combination thereof.
4. The method of claim 2 , wherein the phospholipid is one or more of sphingomyelin, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG).
5. The method of claim 2 , wherein the phospholipid is a mixture of sphingomyelin and dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG).
6. The method of claim 2 , wherein the phospholipid is a mixture of sphingomyelin, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG).
7. The method of claim 5 , wherein the ratio of total peptide to lipid is about 1:about 0.5 to about 1:about 5.
8. The method of claim 6 , wherein the ratio of total peptide to lipid is about 1:about 0.5 to about 1:about 5.
9. The method of claim 6 , wherein the peptide:sphingomyelin:DPPC:DPPG weight ratio is 1:1.2125:1.2125:0.075.
10. The method of claim 1 , wherein the dyslipidemia is hyperproteinemia, high low-density lipoprotein serum concentration, high very low-density lipoprotein serum concentration, hyperlipidemia, low high-density lipoprotein serum concentration, hypocholesterolemia, Abetalipoproteinemia, ApoA-I deficiency, or Tangier disease.
11. The method of claim 1 , wherein the dyslipidemia is hyperlipidemia, hypercholesterolemia, ApoA-I deficiency, or hypertriglyceridemia.