Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1023 - 1033 |
| Number of pages | 11 |
| Journal | Hypertension |
| Volume | 66 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2015 |
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Obligatory role for B cells in the development of angiotensin II-dependent hypertension. / Chan, Christopher Te-Lee; Sobey, Christopher G; Lieu, Maggie; Ferens, Dorota M; Kett, Michelle M; Diep, Henry; Kim, Helena Hyun Ah; Krishnan, Shalini M; Lewis, Caitlin V; Salimova, Ekaterina; Tipping, Peter G; Vinh, Antony; Samuel, Chrishan S; Peter, Karlheinz; Guzik, Tomasz J; Kyaw, Tin S; Toh, Ban-Hock; Bobik, Alexander; Drummond, Grant R.
In: Hypertension, Vol. 66, No. 5, 2015, p. 1023 - 1033.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Obligatory role for B cells in the development of angiotensin II-dependent hypertension
AU - Chan, Christopher Te-Lee
AU - Sobey, Christopher G
AU - Lieu, Maggie
AU - Ferens, Dorota M
AU - Kett, Michelle M
AU - Diep, Henry
AU - Kim, Helena Hyun Ah
AU - Krishnan, Shalini M
AU - Lewis, Caitlin V
AU - Salimova, Ekaterina
AU - Tipping, Peter G
AU - Vinh, Antony
AU - Samuel, Chrishan S
AU - Peter, Karlheinz
AU - Guzik, Tomasz J
AU - Kyaw, Tin S
AU - Toh, Ban-Hock
AU - Bobik, Alexander
AU - Drummond, Grant R
PY - 2015
Y1 - 2015
N2 - Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25 increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80 increase in splenic plasma cell numbers, (3) a 500 increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R-/-) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R-/- (Delta30+/-4 mm Hg) relative to wild-type (Delta41+/-5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R-/- mice displayed reduced IgG accumulation in the aorta, which was associated with 80 fewer aortic macrophages and a 70 reduction in transforming growth factor-beta expression. BAFF-R-/- mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by approximately 35 . Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension.
AB - Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25 increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80 increase in splenic plasma cell numbers, (3) a 500 increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R-/-) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R-/- (Delta30+/-4 mm Hg) relative to wild-type (Delta41+/-5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R-/- mice displayed reduced IgG accumulation in the aorta, which was associated with 80 fewer aortic macrophages and a 70 reduction in transforming growth factor-beta expression. BAFF-R-/- mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by approximately 35 . Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension.
UR - http://hyper.ahajournals.org/content/66/5/1023.full.pdf+html
U2 - 10.1161/HYPERTENSIONAHA.115.05779
DO - 10.1161/HYPERTENSIONAHA.115.05779
M3 - Article
VL - 66
SP - 1023
EP - 1033
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 5
ER -