Inhibition of Vascular Inflammation by Apolipoprotein A-IV
BackgroundApolipoprotein (apo) A-IV, the third most abundant apolipoprotein in human high density lipoproteins (HDLs), inhibits intestinal and systemic inflammation. This study asks if apoA-IV also inhibits acute vascular inflammation.MethodsInflammation was induced in New Zealand White rabbits by p...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.901408/full |
| _version_ | 1818546617352978432 |
|---|---|
| author | Kate Shearston Joanne T. M. Tan Joanne T. M. Tan Blake J. Cochran Kerry-Anne Rye |
| author_facet | Kate Shearston Joanne T. M. Tan Joanne T. M. Tan Blake J. Cochran Kerry-Anne Rye |
| author_sort | Kate Shearston |
| collection | DOAJ |
| description | BackgroundApolipoprotein (apo) A-IV, the third most abundant apolipoprotein in human high density lipoproteins (HDLs), inhibits intestinal and systemic inflammation. This study asks if apoA-IV also inhibits acute vascular inflammation.MethodsInflammation was induced in New Zealand White rabbits by placing a non-occlusive silastic collar around the common carotid artery. A single 1 mg/kg intravenous infusion of lipid-free apoA-IV or saline (control) was administered to the animals 24 h before collar insertion. The animals were euthanised 24 h post-collar insertion. Human coronary artery cells (HCAECs) were pre-incubated with reconstituted HDLs containing apoA-IV complexed with phosphatidylcholine, (A-IV)rHDLs, then activated by incubation with tumour necrosis factor (TNF)-α. Cell surface vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the TNF-α-activated HCAECs was quantified by flow cytometry. VCAM-1, ICAM-1 and 3β-hydroxysteroid-Δ24 reductase (DHCR24) mRNA levels were quantified by real time PCR.ResultsApolipoprotein ApoA-IV treatment significantly decreased collar-induced endothelial expression of VCAM-1, ICAM-1 and neutrophil infiltration into the arterial intima by 67.6 ± 9.9% (p < 0.01), 75.4 ± 6.9% (p < 0.01) and 74.4 ± 8.5% (p < 0.05), respectively. It also increased endothelial expression of DHCR24 by 2.6-fold (p < 0.05). Pre-incubation of HCAECs with (A-IV)rHDLs prior to stimulation with TNF-α inhibited VCAM-1 and ICAM-1 protein levels by 62.2 ± 12.1% and 33.7 ± 5.7%, respectively. VCAM-1 and ICAM-1 mRNA levels were decreased by 55.8 ± 7.2% and 49.6 ± 7.9%, respectively, while DHCR24 mRNA expression increased by threefold. Transfection of HCAECs with DHCR24 siRNA attenuated the anti-inflammatory effects of (A-IV)rHDLs. Pre-incubation of TNF-α-activated HCAECs with (A-IV)rHDLs also inhibited nuclear translocation of the p65 subunit of nuclear factor-κB (NF-κB), and decreased IκBα phosphorylation.ConclusionThese results indicate that apoA-IV inhibits vascular inflammation in vitro and in vivo by inhibiting NF-κB activation in a DHCR24-dependent manner. |
| first_indexed | 2024-12-12T07:55:37Z |
| format | Article |
| id | doaj.art-02d7e6fc771a4076a3bb0a0079eb6d34 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-12T07:55:37Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-02d7e6fc771a4076a3bb0a0079eb6d342022-12-22T00:32:20ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.901408901408Inhibition of Vascular Inflammation by Apolipoprotein A-IVKate Shearston0Joanne T. M. Tan1Joanne T. M. Tan2Blake J. Cochran3Kerry-Anne Rye4Lipid Research Group, Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW, AustraliaVascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, AustraliaAdelaide Medical School, The University of Adelaide, Adelaide, SA, AustraliaLipid Research Group, Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW, AustraliaLipid Research Group, Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW, AustraliaBackgroundApolipoprotein (apo) A-IV, the third most abundant apolipoprotein in human high density lipoproteins (HDLs), inhibits intestinal and systemic inflammation. This study asks if apoA-IV also inhibits acute vascular inflammation.MethodsInflammation was induced in New Zealand White rabbits by placing a non-occlusive silastic collar around the common carotid artery. A single 1 mg/kg intravenous infusion of lipid-free apoA-IV or saline (control) was administered to the animals 24 h before collar insertion. The animals were euthanised 24 h post-collar insertion. Human coronary artery cells (HCAECs) were pre-incubated with reconstituted HDLs containing apoA-IV complexed with phosphatidylcholine, (A-IV)rHDLs, then activated by incubation with tumour necrosis factor (TNF)-α. Cell surface vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the TNF-α-activated HCAECs was quantified by flow cytometry. VCAM-1, ICAM-1 and 3β-hydroxysteroid-Δ24 reductase (DHCR24) mRNA levels were quantified by real time PCR.ResultsApolipoprotein ApoA-IV treatment significantly decreased collar-induced endothelial expression of VCAM-1, ICAM-1 and neutrophil infiltration into the arterial intima by 67.6 ± 9.9% (p < 0.01), 75.4 ± 6.9% (p < 0.01) and 74.4 ± 8.5% (p < 0.05), respectively. It also increased endothelial expression of DHCR24 by 2.6-fold (p < 0.05). Pre-incubation of HCAECs with (A-IV)rHDLs prior to stimulation with TNF-α inhibited VCAM-1 and ICAM-1 protein levels by 62.2 ± 12.1% and 33.7 ± 5.7%, respectively. VCAM-1 and ICAM-1 mRNA levels were decreased by 55.8 ± 7.2% and 49.6 ± 7.9%, respectively, while DHCR24 mRNA expression increased by threefold. Transfection of HCAECs with DHCR24 siRNA attenuated the anti-inflammatory effects of (A-IV)rHDLs. Pre-incubation of TNF-α-activated HCAECs with (A-IV)rHDLs also inhibited nuclear translocation of the p65 subunit of nuclear factor-κB (NF-κB), and decreased IκBα phosphorylation.ConclusionThese results indicate that apoA-IV inhibits vascular inflammation in vitro and in vivo by inhibiting NF-κB activation in a DHCR24-dependent manner.https://www.frontiersin.org/articles/10.3389/fcvm.2022.901408/fullapolipoprotein A-IVinflammationhigh-density lipoproteinsendothelial cellsnuclear factor-kappaB3β-hydroxysteroid-Δ24 reductase |
| spellingShingle | Kate Shearston Joanne T. M. Tan Joanne T. M. Tan Blake J. Cochran Kerry-Anne Rye Inhibition of Vascular Inflammation by Apolipoprotein A-IV Frontiers in Cardiovascular Medicine apolipoprotein A-IV inflammation high-density lipoproteins endothelial cells nuclear factor-kappaB 3β-hydroxysteroid-Δ24 reductase |
| title | Inhibition of Vascular Inflammation by Apolipoprotein A-IV |
| title_full | Inhibition of Vascular Inflammation by Apolipoprotein A-IV |
| title_fullStr | Inhibition of Vascular Inflammation by Apolipoprotein A-IV |
| title_full_unstemmed | Inhibition of Vascular Inflammation by Apolipoprotein A-IV |
| title_short | Inhibition of Vascular Inflammation by Apolipoprotein A-IV |
| title_sort | inhibition of vascular inflammation by apolipoprotein a iv |
| topic | apolipoprotein A-IV inflammation high-density lipoproteins endothelial cells nuclear factor-kappaB 3β-hydroxysteroid-Δ24 reductase |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.901408/full |
| work_keys_str_mv | AT kateshearston inhibitionofvascularinflammationbyapolipoproteinaiv AT joannetmtan inhibitionofvascularinflammationbyapolipoproteinaiv AT joannetmtan inhibitionofvascularinflammationbyapolipoproteinaiv AT blakejcochran inhibitionofvascularinflammationbyapolipoproteinaiv AT kerryannerye inhibitionofvascularinflammationbyapolipoproteinaiv |