Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1 - 12 |
| Number of pages | 12 |
| Journal | PLoS ONE |
| Volume | 8 |
| Issue number | 4 (Art. ID: e60430) |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
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BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE{-/-} mice. / Kyaw, Tin Soe; Cui, Peng; Tay, Christopher; Kanellakis, Peter; Hosseini, Hamid; Liu, Edgar; Rolink, Antonius G; Tipping, Peter George; Bobik, Alexander; Toh, Ban-Hock.
In: PLoS ONE, Vol. 8, No. 4 (Art. ID: e60430), 2013, p. 1 - 12.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE{-/-} mice
AU - Kyaw, Tin Soe
AU - Cui, Peng
AU - Tay, Christopher
AU - Kanellakis, Peter
AU - Hosseini, Hamid
AU - Liu, Edgar
AU - Rolink, Antonius G
AU - Tipping, Peter George
AU - Bobik, Alexander
AU - Toh, Ban-Hock
PY - 2013
Y1 - 2013
N2 - Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE(-/-) mouse. METHODS AND RESULTS: To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE(-/-) mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93(-) CD19(+) B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19(+) B cells, CD4(+) and CD8(+) T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1beta, TNFalpha, and IFNgamma in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE(-/-) mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93(-) CD19(+) B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. CONCLUSION: Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE(-/-) mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases.
AB - Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE(-/-) mouse. METHODS AND RESULTS: To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE(-/-) mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93(-) CD19(+) B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19(+) B cells, CD4(+) and CD8(+) T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1beta, TNFalpha, and IFNgamma in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE(-/-) mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93(-) CD19(+) B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. CONCLUSION: Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE(-/-) mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases.
UR - http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0060430&representation=PDF
U2 - 10.1371/journal.pone.0060430
DO - 10.1371/journal.pone.0060430
M3 - Article
VL - 8
SP - 1
EP - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4 (Art. ID: e60430)
ER -