HDL improves cholesterol and glucose homeostasis and reduces Aatherosclerosis in diabetes-associated atherosclerosis

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dc.contributor.authorDi Bartolo, B.A.
dc.contributor.authorCartland, S.P.
dc.contributor.authorGenner, S.
dc.contributor.authorManuneedhi Cholan, P.
dc.contributor.authorVellozzi, M.
dc.contributor.authorRye, K.A.
dc.contributor.authorKavurma, M.M.
dc.contributor.editorSasso, F.C.
dc.date.issued2021
dc.description.abstractBackground and Aims. Apolipoprotein A-I (ApoA-I), the main component of high-density lipoprotein (HDL), not only promotes reverse cholesterol transport (RCT) in atherosclerosis but also increases insulin secretion in pancreatic β-cells, suggesting that interventions which raise HDL levels may be beneficial in diabetes-associated cardiovascular disease (CVD). Previously, we showed that TNF-related apoptosis-inducing ligand (TRAIL) deletion in Apolipoprotein Eknockout (Apoe-/-) mice results in diabetes-accelerated atherosclerosis in response to a “Western” diet. Here, we sought to identify whether reconstituted HDL (rHDL) could improve features of diabetes-associated CVD in Trail-/-Apoe-/- mice. Methods and Results. Trail-/-Apoe-/- and Apoe-/- mice on a “Western” diet for 12 weeks received 3 weekly infusions of either PBS (vehicle) or rHDL (containing ApoA-I (20 mg/kg) and 1-palmitoyl-2-linoleoyl phosphatidylcholine). Administration of rHDL reduced total plasma cholesterol, triglyceride, and glucose levels in Trail-/-Apoe-/- but not in Apoe-/- mice, with no change in weight gain observed. rHDL treatment also improved glucose clearance in response to insulin and glucose tolerance tests. Immunohistological analysis of pancreata revealed increased insulin expression/production and a reduction in macrophage infiltration in mice with TRAIL deletion. Furthermore, atherosclerotic plaque size in Trail-/-Apoe-/- mice was significantly reduced associating with increased expression of the M2 macrophage marker CD206, suggesting HDL's involvement in the polarization of macrophages. rHDL also increased vascular mRNA expression of RCT transporters, ABCA1 and ABCG1, in Trail-/-Apoe-/- but not in Apoe-/- mice. Conclusions. rHDL improves features of diabetes-associated atherosclerosis in mice. These findings support the therapeutic potential of rHDL in the treatment of atherosclerosis and associated diabetic complications. More studies are warranted to understand rHDL’s mechanism of action.
dc.description.statementofresponsibilityBelinda A. Di Bartolo, Siân P. Cartland, Scott Genner, Pradeep Manuneedhi Cholan, Melissa Vellozzi, Kerry-Anne Rye and Mary M. Kavurma
dc.identifier.citationJournal of Diabetes Research, 2021; 2021:1-10
dc.identifier.doi10.1155/2021/6668506
dc.identifier.issn2314-6745
dc.identifier.issn2314-6753
dc.identifier.orcidDi Bartolo, B.A. [0000-0001-8420-0461]
dc.identifier.urihttp://hdl.handle.net/2440/131466
dc.language.isoen
dc.publisherHindawi
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1037074
dc.rights© 2021 Belinda A. Di Bartolo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1155/2021/6668506
dc.subjectMacrophages
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectDiabetes Mellitus
dc.subjectDisease Models, Animal
dc.subjectCholesterol
dc.subjectBlood Glucose
dc.subjectLipoproteins, HDL
dc.subjectPhosphatidylcholines
dc.subjectApolipoprotein A-I
dc.subjectAnticholesteremic Agents
dc.subjectHypoglycemic Agents
dc.subjectHomeostasis
dc.subjectMale
dc.subjectDyslipidemias
dc.subjectAtherosclerosis
dc.subjectTNF-Related Apoptosis-Inducing Ligand
dc.subjectPlaque, Atherosclerotic
dc.subjectATP Binding Cassette Transporter 1
dc.subjectDiet, Western
dc.subjectBiomarkers
dc.subjectMice, Knockout, ApoE
dc.subjectATP Binding Cassette Transporter, Subfamily G, Member 1
dc.titleHDL improves cholesterol and glucose homeostasis and reduces Aatherosclerosis in diabetes-associated atherosclerosis
dc.typeJournal article
pubs.publication-statusPublished

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