Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice
Bacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dos...
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2022-10-01
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| author | Siroon Bekkering Krishan Singh Hui Lu Albert P. Limawan Claudia A. Nold-Petry Megan J. Wallace Nigel Curtis Salvatore Pepe Michael Cheung David P. Burgner Timothy Moss |
| author_facet | Siroon Bekkering Krishan Singh Hui Lu Albert P. Limawan Claudia A. Nold-Petry Megan J. Wallace Nigel Curtis Salvatore Pepe Michael Cheung David P. Burgner Timothy Moss |
| author_sort | Siroon Bekkering |
| collection | DOAJ |
| description | Bacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dosing schedule, and route of administration. We aimed to elucidate the effect of neonatal subcutaneous BCG vaccination—analogous to human BCG vaccination—on atherosclerosis development in <i>ApoE<sup>−/−</sup></i> mice. At 2 days of age, a total of 40 <i>ApoE<sup>−/−</sup></i> mice received either a weight-equivalent human dose of BCG, or saline, subcutaneously. From 4 weeks onwards, the mice were fed a Western-type diet containing 22% fat. At 16 weeks of age, mice were sacrificed for the assessment of atherosclerosis. Body weight, plasma lipids, atherosclerosis lesion size and collagen content were similar in both groups. Atherosclerosis lesion number was lower in mice that received BCG. Macrophage content was 20% lower in the BCG-vaccinated mice (<i>p</i> < 0.05), whereas plaque lipid content was increased by 25% (<i>p</i> < 0.01). In conclusion, neonatal BCG vaccination reduces atherosclerosis plaque number and macrophage content but increases lipid content in a murine model of atherosclerosis. Human epidemiological and mechanistic studies are warranted to investigate whether neonatal BCG vaccination is potentially atheroprotective. |
| first_indexed | 2024-03-09T20:39:57Z |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T20:39:57Z |
| publishDate | 2022-10-01 |
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| series | Biology |
| spelling | doaj.art-85c03467002f447bb7b415ace35b59542023-11-23T23:00:48ZengMDPI AGBiology2079-77372022-10-011110151110.3390/biology11101511Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> MiceSiroon Bekkering0Krishan Singh1Hui Lu2Albert P. Limawan3Claudia A. Nold-Petry4Megan J. Wallace5Nigel Curtis6Salvatore Pepe7Michael Cheung8David P. Burgner9Timothy Moss10Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, AustraliaSchool of Public Health and Preventive Medicine, Monash University, Clayton, VIC 3800, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaBacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dosing schedule, and route of administration. We aimed to elucidate the effect of neonatal subcutaneous BCG vaccination—analogous to human BCG vaccination—on atherosclerosis development in <i>ApoE<sup>−/−</sup></i> mice. At 2 days of age, a total of 40 <i>ApoE<sup>−/−</sup></i> mice received either a weight-equivalent human dose of BCG, or saline, subcutaneously. From 4 weeks onwards, the mice were fed a Western-type diet containing 22% fat. At 16 weeks of age, mice were sacrificed for the assessment of atherosclerosis. Body weight, plasma lipids, atherosclerosis lesion size and collagen content were similar in both groups. Atherosclerosis lesion number was lower in mice that received BCG. Macrophage content was 20% lower in the BCG-vaccinated mice (<i>p</i> < 0.05), whereas plaque lipid content was increased by 25% (<i>p</i> < 0.01). In conclusion, neonatal BCG vaccination reduces atherosclerosis plaque number and macrophage content but increases lipid content in a murine model of atherosclerosis. Human epidemiological and mechanistic studies are warranted to investigate whether neonatal BCG vaccination is potentially atheroprotective.https://www.mdpi.com/2079-7737/11/10/1511atherosclerosisneonatal vaccinationBCGinflammation<i>ApoE</i><sup>−/−</sup> |
| spellingShingle | Siroon Bekkering Krishan Singh Hui Lu Albert P. Limawan Claudia A. Nold-Petry Megan J. Wallace Nigel Curtis Salvatore Pepe Michael Cheung David P. Burgner Timothy Moss Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice Biology atherosclerosis neonatal vaccination BCG inflammation <i>ApoE</i><sup>−/−</sup> |
| title | Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice |
| title_full | Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice |
| title_fullStr | Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice |
| title_full_unstemmed | Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice |
| title_short | Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in <i>ApoE</i><sup>−/−</sup> Mice |
| title_sort | neonatal subcutaneous bcg vaccination decreases atherosclerotic plaque number and plaque macrophage content in i apoe i sup sup mice |
| topic | atherosclerosis neonatal vaccination BCG inflammation <i>ApoE</i><sup>−/−</sup> |
| url | https://www.mdpi.com/2079-7737/11/10/1511 |
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