Abstract 074: An Obligatory Role for B Cells in the Development of Angiotensin II-dependent Hypertension
Background: Clinical hypertension is associated with raised serum antibody levels. However, no studies have examined whether B cells and antibodies play causative roles in the pathogenesis of hypertension. We investigated whether experimental hypertension is similarly associated with elevated IgG production, and if B cell/antibody deficiency affords protection against hypertension and associated vascular remodeling.
Methods and Results: Ang II-dependent hypertension in mice was associated with B cell activation/maturation as revealed by a: (1) a 25% increase in the proportion of splenic B cells that expressed the activation marker CD86; (2) an 80% increase in numbers of splenic plasma cells, (3) a 500% increase in serum IgG levels; and (4) marked accumulation of IgG deposits in the aortic adventitia. Indicative of a causative role for B cells, B cell activating factor-receptor-deficient (BAFF-R-/-) mice, which lack mature B cells, displayed blunted hypertensive responses to chronic angiotensin II infusion (Δ30±4 mmHg) compared to wild-type (WT) mice (Δ41±5 mmHg). Importantly, adoptive transfer of B cells into BAFF-R-/- mice restored the hypertensive response. BAFF-R-/- mice showed no evidence of Ang II-induced increases in aortic IgG accumulation. They also had 80% fewer F4/80+ macrophages, 60% fewer CD4+ T cells, and 70% reduction in TGF-β expression and collagen in their aortas compared to Ang II-treated wild-type mice. Ang II doubled aortic pulse-wave velocity, a measure of vessel stiffening, whereas BAFF-R-/- mice were largely protected (70% reduced) from this effect. Finally, pharmacological depletion of B cells with an anti-CD20 antibody blunted Ang II-induced hypertension (Δ37±9 mmHg vs Δ57±6 mmHg).
Conclusions: We provide the first evidence that B cells are activated during development of hypertension and contribute to vessel remodeling and elevated blood pressure. These findings suggest B cells and/or the IgG antibodies they produce could be targeted for anti-hypertensive therapy.
Author Disclosures: C. Chan: None. C. Sobey: None. M. Lieu: None. D. Ferens: None. M. Kett: None. H. Diep: None. H. Kim: None. S. Krishnan: None. E. Salimova: None. A. Vinh: None. C. Samuel: None. P. Tipping: None. T. Kyaw: None. B. Toh: None. A. Bobik: None. G. Drummond: None.
- © 2015 by American Heart Association, Inc.