Reverse D4F, an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in ApoE-null Mice
Objective:Synthetic class A amphipathic helical peptide analogs of apolipoprotein-AI (apoAI; with varied phenylalanine residues) are emerging therapeutic approaches under investigation for atherosclerosis. Utilizing retroinverso sequencing, we designed reverse-D4F (Rev-D4F) peptide with 18 d-amino a...
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Veröffentlicht in: | Journal of cardiovascular pharmacology and therapeutics 2012-09, Vol.17 (3), p.334-343 |
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container_title | Journal of cardiovascular pharmacology and therapeutics |
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creator | Qin, Shucun Kamanna, Vaijinath S. Lai, Jack H. Liu, Tianjiao Ganji, Shobha H. Zhang, Linhua Bachovchin, William W. Kashyap, Moti L. |
description | Objective:Synthetic class A amphipathic helical peptide analogs of apolipoprotein-AI (apoAI; with varied phenylalanine residues) are emerging therapeutic approaches under investigation for atherosclerosis. Utilizing retroinverso sequencing, we designed reverse-D4F (Rev-D4F) peptide with 18 d-amino acids containing 4 phenylalanine residues and reverse order that allows the side chain residues to be of exact alignment and superimposable to those of the parent l-amino acid peptide. This study examined the effect of Rev-D4F on atherosclerosis in apolipoprotein E (apoE)-null mice and the underlying mechanisms.
Materials/Methods:ApoE-null mice were fed a chow diet and administered water (control), Rev-D4F, or L4F mimetic peptides (0.4 mg/mL, equivalent to 1.6 mg/d) orally in drinking water for 6 weeks. Aortic root atherosclerotic lesion area, lesion macrophage content, and the ability of plasma high-density lipoprotein (HDL) to influence monocyte chemotaxis were measured.
Results:Rev-D4F significantly decreased aortic sinus atherosclerotic lesion area and lesion macrophage content without affecting plasma total and HDL-cholesterol levels in apoE-null mice. The HDL from Rev-D4F-treated mice showed enhanced anti-inflammatory monocyte chemotactic activity, while low-density lipoprotein (LDL) exhibited reduced proinflammatory activity. In in vitro studies, Rev-D4F inhibited LDL oxidation, endothelial cell vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic factor 1 (MCP-1) expression, and monocyte adhesion to aortic endothelial cells.
Conclusions:The Rev-D4F inhibits atherosclerosis by inhibiting endothelial inflammatory/oxidative events and improving HDL function. The data suggest that Rev-D4F may be an effective apoAI mimetic peptide for further development in preventing atherosclerosis. |
doi_str_mv | 10.1177/1074248411434598 |
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Materials/Methods:ApoE-null mice were fed a chow diet and administered water (control), Rev-D4F, or L4F mimetic peptides (0.4 mg/mL, equivalent to 1.6 mg/d) orally in drinking water for 6 weeks. Aortic root atherosclerotic lesion area, lesion macrophage content, and the ability of plasma high-density lipoprotein (HDL) to influence monocyte chemotaxis were measured.
Results:Rev-D4F significantly decreased aortic sinus atherosclerotic lesion area and lesion macrophage content without affecting plasma total and HDL-cholesterol levels in apoE-null mice. The HDL from Rev-D4F-treated mice showed enhanced anti-inflammatory monocyte chemotactic activity, while low-density lipoprotein (LDL) exhibited reduced proinflammatory activity. In in vitro studies, Rev-D4F inhibited LDL oxidation, endothelial cell vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic factor 1 (MCP-1) expression, and monocyte adhesion to aortic endothelial cells.
Conclusions:The Rev-D4F inhibits atherosclerosis by inhibiting endothelial inflammatory/oxidative events and improving HDL function. The data suggest that Rev-D4F may be an effective apoAI mimetic peptide for further development in preventing atherosclerosis.</description><identifier>ISSN: 1074-2484</identifier><identifier>EISSN: 1940-4034</identifier><identifier>DOI: 10.1177/1074248411434598</identifier><identifier>PMID: 22308547</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Aorta - cytology ; Apolipoprotein A-I - pharmacology ; Apolipoproteins E - genetics ; Apolipoproteins E - metabolism ; Atherosclerosis - prevention & control ; Body Weight - drug effects ; Chemokine CCL2 - genetics ; Chemokine CCL2 - metabolism ; Coculture Techniques ; Endothelial Cells ; Female ; Humans ; Lipids - blood ; Macrophages - drug effects ; Mice ; Mice, Knockout ; Peptides - pharmacology</subject><ispartof>Journal of cardiovascular pharmacology and therapeutics, 2012-09, Vol.17 (3), p.334-343</ispartof><rights>The Author(s) 2012</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-b5366541ff0231a07a508ed3c7dbd221470188d78255b2b371fa75800fa85503</citedby><cites>FETCH-LOGICAL-c337t-b5366541ff0231a07a508ed3c7dbd221470188d78255b2b371fa75800fa85503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1074248411434598$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1074248411434598$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21966,27853,27924,27925,44945,45333</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/1074248411434598?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22308547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qin, Shucun</creatorcontrib><creatorcontrib>Kamanna, Vaijinath S.</creatorcontrib><creatorcontrib>Lai, Jack H.</creatorcontrib><creatorcontrib>Liu, Tianjiao</creatorcontrib><creatorcontrib>Ganji, Shobha H.</creatorcontrib><creatorcontrib>Zhang, Linhua</creatorcontrib><creatorcontrib>Bachovchin, William W.</creatorcontrib><creatorcontrib>Kashyap, Moti L.</creatorcontrib><title>Reverse D4F, an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in ApoE-null Mice</title><title>Journal of cardiovascular pharmacology and therapeutics</title><addtitle>J Cardiovasc Pharmacol Ther</addtitle><description>Objective:Synthetic class A amphipathic helical peptide analogs of apolipoprotein-AI (apoAI; with varied phenylalanine residues) are emerging therapeutic approaches under investigation for atherosclerosis. Utilizing retroinverso sequencing, we designed reverse-D4F (Rev-D4F) peptide with 18 d-amino acids containing 4 phenylalanine residues and reverse order that allows the side chain residues to be of exact alignment and superimposable to those of the parent l-amino acid peptide. This study examined the effect of Rev-D4F on atherosclerosis in apolipoprotein E (apoE)-null mice and the underlying mechanisms.
Materials/Methods:ApoE-null mice were fed a chow diet and administered water (control), Rev-D4F, or L4F mimetic peptides (0.4 mg/mL, equivalent to 1.6 mg/d) orally in drinking water for 6 weeks. Aortic root atherosclerotic lesion area, lesion macrophage content, and the ability of plasma high-density lipoprotein (HDL) to influence monocyte chemotaxis were measured.
Results:Rev-D4F significantly decreased aortic sinus atherosclerotic lesion area and lesion macrophage content without affecting plasma total and HDL-cholesterol levels in apoE-null mice. The HDL from Rev-D4F-treated mice showed enhanced anti-inflammatory monocyte chemotactic activity, while low-density lipoprotein (LDL) exhibited reduced proinflammatory activity. In in vitro studies, Rev-D4F inhibited LDL oxidation, endothelial cell vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic factor 1 (MCP-1) expression, and monocyte adhesion to aortic endothelial cells.
Conclusions:The Rev-D4F inhibits atherosclerosis by inhibiting endothelial inflammatory/oxidative events and improving HDL function. The data suggest that Rev-D4F may be an effective apoAI mimetic peptide for further development in preventing atherosclerosis.</description><subject>Animals</subject><subject>Aorta - cytology</subject><subject>Apolipoprotein A-I - pharmacology</subject><subject>Apolipoproteins E - genetics</subject><subject>Apolipoproteins E - metabolism</subject><subject>Atherosclerosis - prevention & control</subject><subject>Body Weight - drug effects</subject><subject>Chemokine CCL2 - genetics</subject><subject>Chemokine CCL2 - metabolism</subject><subject>Coculture Techniques</subject><subject>Endothelial Cells</subject><subject>Female</subject><subject>Humans</subject><subject>Lipids - blood</subject><subject>Macrophages - drug effects</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Peptides - pharmacology</subject><issn>1074-2484</issn><issn>1940-4034</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1Lw0AQxRdRbK3ePUmOHhqd_epuj6W2Wqgo0quETTKxW_JlNhH8793Y6kHwMjMwv_eYeYRcUrihVKlbCkowoQWlggs51UdkSKcCQgFcHPvZr8N-PyBnzu0AoKdOyYAxDloKNSSvL_iBjcPgTizHgSmDWV3ltq7qpmrRluFsFTzaAlubBM9YtzbFcbAqtza2rQtm7RabyiV5X60L7Ld8EZZdnntZgufkJDO5w4tDH5HNcrGZP4Trp_vVfLYOE85VG8aSTyZS0CwDxqkBZSRoTHmi0jhljAoFVOtUaSZlzGKuaGaU1ACZ0VICH5Hrva2_-r1D10aFdQnmuSmx6lxEgXPq42Hao7BHE3-yazCL6sYWpvn0UNRnGv3N1EuuDu5dXGD6K_gJ0QPhHnDmDaNd1TWlf_Z_wy8T1XvR</recordid><startdate>201209</startdate><enddate>201209</enddate><creator>Qin, Shucun</creator><creator>Kamanna, Vaijinath S.</creator><creator>Lai, Jack H.</creator><creator>Liu, Tianjiao</creator><creator>Ganji, Shobha H.</creator><creator>Zhang, Linhua</creator><creator>Bachovchin, William W.</creator><creator>Kashyap, Moti L.</creator><general>SAGE Publications</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201209</creationdate><title>Reverse D4F, an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in ApoE-null Mice</title><author>Qin, Shucun ; Kamanna, Vaijinath S. ; Lai, Jack H. ; Liu, Tianjiao ; Ganji, Shobha H. ; Zhang, Linhua ; Bachovchin, William W. ; Kashyap, Moti L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-b5366541ff0231a07a508ed3c7dbd221470188d78255b2b371fa75800fa85503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Aorta - cytology</topic><topic>Apolipoprotein A-I - pharmacology</topic><topic>Apolipoproteins E - genetics</topic><topic>Apolipoproteins E - metabolism</topic><topic>Atherosclerosis - prevention & control</topic><topic>Body Weight - drug effects</topic><topic>Chemokine CCL2 - genetics</topic><topic>Chemokine CCL2 - metabolism</topic><topic>Coculture Techniques</topic><topic>Endothelial Cells</topic><topic>Female</topic><topic>Humans</topic><topic>Lipids - blood</topic><topic>Macrophages - drug effects</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Peptides - pharmacology</topic><toplevel>online_resources</toplevel><creatorcontrib>Qin, Shucun</creatorcontrib><creatorcontrib>Kamanna, Vaijinath S.</creatorcontrib><creatorcontrib>Lai, Jack H.</creatorcontrib><creatorcontrib>Liu, Tianjiao</creatorcontrib><creatorcontrib>Ganji, Shobha H.</creatorcontrib><creatorcontrib>Zhang, Linhua</creatorcontrib><creatorcontrib>Bachovchin, William W.</creatorcontrib><creatorcontrib>Kashyap, Moti L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cardiovascular pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Qin, Shucun</au><au>Kamanna, Vaijinath S.</au><au>Lai, Jack H.</au><au>Liu, Tianjiao</au><au>Ganji, Shobha H.</au><au>Zhang, Linhua</au><au>Bachovchin, William W.</au><au>Kashyap, Moti L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reverse D4F, an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in ApoE-null Mice</atitle><jtitle>Journal of cardiovascular pharmacology and therapeutics</jtitle><addtitle>J Cardiovasc Pharmacol Ther</addtitle><date>2012-09</date><risdate>2012</risdate><volume>17</volume><issue>3</issue><spage>334</spage><epage>343</epage><pages>334-343</pages><issn>1074-2484</issn><eissn>1940-4034</eissn><abstract>Objective:Synthetic class A amphipathic helical peptide analogs of apolipoprotein-AI (apoAI; with varied phenylalanine residues) are emerging therapeutic approaches under investigation for atherosclerosis. Utilizing retroinverso sequencing, we designed reverse-D4F (Rev-D4F) peptide with 18 d-amino acids containing 4 phenylalanine residues and reverse order that allows the side chain residues to be of exact alignment and superimposable to those of the parent l-amino acid peptide. This study examined the effect of Rev-D4F on atherosclerosis in apolipoprotein E (apoE)-null mice and the underlying mechanisms.
Materials/Methods:ApoE-null mice were fed a chow diet and administered water (control), Rev-D4F, or L4F mimetic peptides (0.4 mg/mL, equivalent to 1.6 mg/d) orally in drinking water for 6 weeks. Aortic root atherosclerotic lesion area, lesion macrophage content, and the ability of plasma high-density lipoprotein (HDL) to influence monocyte chemotaxis were measured.
Results:Rev-D4F significantly decreased aortic sinus atherosclerotic lesion area and lesion macrophage content without affecting plasma total and HDL-cholesterol levels in apoE-null mice. The HDL from Rev-D4F-treated mice showed enhanced anti-inflammatory monocyte chemotactic activity, while low-density lipoprotein (LDL) exhibited reduced proinflammatory activity. In in vitro studies, Rev-D4F inhibited LDL oxidation, endothelial cell vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic factor 1 (MCP-1) expression, and monocyte adhesion to aortic endothelial cells.
Conclusions:The Rev-D4F inhibits atherosclerosis by inhibiting endothelial inflammatory/oxidative events and improving HDL function. The data suggest that Rev-D4F may be an effective apoAI mimetic peptide for further development in preventing atherosclerosis.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>22308547</pmid><doi>10.1177/1074248411434598</doi><tpages>10</tpages></addata></record> |
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subjects | Animals Aorta - cytology Apolipoprotein A-I - pharmacology Apolipoproteins E - genetics Apolipoproteins E - metabolism Atherosclerosis - prevention & control Body Weight - drug effects Chemokine CCL2 - genetics Chemokine CCL2 - metabolism Coculture Techniques Endothelial Cells Female Humans Lipids - blood Macrophages - drug effects Mice Mice, Knockout Peptides - pharmacology |
title | Reverse D4F, an Apolipoprotein-AI Mimetic Peptide, Inhibits Atherosclerosis in ApoE-null Mice |
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