Abstract
Obesity has achieved epidemic status in the United States, resulting in an increase in type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease. Numerous studies have shown that inflammation plays a key role in the development of insulin resistance and diabetic complications. HDL cholesterol levels are inversely associated with coronary heart disease in humans. The beneficial effect of HDL is due, in part, to apolipoproteins A-I and E, which possess anti-inflammatory properties. The functional quality of HDL, however, may be reduced in the context of diabetes. Thus, raising levels of functional HDL is an important target for reducing inflammation and diabetic complications. Apo A-I possesses eight alpha-helical sequences, most of which form class A amphipathic helical structures. Peptides belonging to this class inhibit atherogenesis in several mouse models. Additional peptides based on structural components of apoE have been shown to mediate a rapid clearance of atherogenic lipoproteins in dyslipidemic mice. In this review, we discuss the efficacy of apolipoprotein mimetic peptides in improving lipoprotein function, reducing inflammation, and reversing insulin resistance and cardiometabolic disease processes in diabetic animals.
Highlights
Obesity has achieved epidemic status in the United States, resulting in an increase in type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease
Medications such as statins, fibrates, niacin, and thiazolidinediones have been used to treat lipid and lipoprotein abnormalities associated with insulin resistance and type 2 diabetes, resulting in significant improvement in coronary artery disease after diabetic dyslipidemia treatment [2,3]
We observed that the 5F peptide inhibited lesion formation in mice adFurthermore, when was isolated from mice administered a high-fat diet injected ministered a high-fat diet by a mechanism that does not involve changes in the lipoprotein with 5F and presented to human artery wall endothelial cells in vitro together with human low-density lipoprotein (LDL), there were substantially fewer lipid hydroperoxides formed
Summary
Modes of treatment of diabetic dyslipidemia include clearance of atherogenic lipoproof treatment of diabetic dyslipidemia include clearance of to atherogenic teinsModes to correct dyslipidemia and inhibition of oxidative stress due increased lipolipid proteins to correct[30]. We observed that the 5F peptide inhibited lesion formation in mice adFurthermore, when was isolated from mice administered a high-fat diet injected ministered a high-fat diet by a mechanism that does not involve changes in the lipoprotein with 5F and presented to human artery wall endothelial cells in vitro together with human low-density lipoprotein (LDL), there were substantially fewer lipid hydroperoxides formed This resulted in substantially lower LDL-induced monocyte chemotactic activity than with. The peptide with only 18 amino acid residues was shown to possess anti-inflammatory properties [33] Based on these observations, Abraham and coworkers used the 4F analog of apoA-I mimetic peptide to study effects of peptide administration on hyperglycemia, obesity, and metabolic syndrome using animal models of diabetes [34,35]. In all of the studies performed with apoA-I mimetic peptides, plasma cholesterol was not reduced, and no changes in the levels of atherogenic lipoproteins or cholesterol profiles were observed, despite beneficial effects on the diabetes-mediated oxidative stress
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