{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:56:52Z","timestamp":1775537812892,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Depletion of mature B cells affords protection against experimental hypertension. However, whether B cell-mediated hypertension is dependent on differentiation into antibody-secreting cells (ASCs) remains unclear. Using the proteasome inhibitor, bortezomib, the present study tested the effect of ASC reduction on angiotensin II-induced hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL6\/J mice were infused with angiotensin II (0.7\u2005mg\/kg\/day; s.c.) for 28 days via osmotic minipump to induce hypertension. Normotensive control mice received saline infusion. Bortezomib (750\u2005\u03bcg\/kg) or vehicle (0.1% DMSO) was administered (i.v.) 3 days prior to minipump implantation, and twice weekly thereafter. Systolic blood pressure was measured weekly using tail-cuff plethysmography. Spleen and bone marrow B1 (CD19<jats:sup>+<\/jats:sup>B220<jats:sup>\u2212<\/jats:sup>), B2 (B220<jats:sup>+<\/jats:sup>CD19<jats:sup>+<\/jats:sup>) and ASCs (CD138<jats:sup>hi<\/jats:sup>Sca-1<jats:sup>+<\/jats:sup>Blimp-1<jats:sup>+<\/jats:sup>) were enumerated by flow cytometry. Serum immunoglobulins were quantified using a bead-based immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bortezomib treatment reduced splenic ASCs by \u223c68% and \u223c64% compared to vehicle treatment in normotensive (2.00\u2009\u00b1\u20090.30 vs. 0.64\u2009\u00b1\u20090.15\u2009\u00d7\u200910<jats:sup>5<\/jats:sup> cells; <jats:italic>n<\/jats:italic>\u2009=\u200910\u201311) and hypertensive mice (0.52\u2009\u00b1\u20090.11 vs. 0.14\u2009\u00b1\u20090.02\u2009\u00d7\u200910<jats:sup>5<\/jats:sup> cells; <jats:italic>n<\/jats:italic>\u2009=\u20099\u201311), respectively. Bone marrow ASCs were also reduced by bortezomib in both normotensive (4.75\u2009\u00b1\u20091.53 vs. 1.71\u2009\u00b1\u20090.41\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> cells; <jats:italic>n<\/jats:italic>\u2009=\u20099\u201311) and hypertensive mice (4.12\u2009\u00b1\u20090.82 vs. 0.89\u2009\u00b1\u20090.18\u2009\u00d7\u200910<jats:sup>3<\/jats:sup> cells; <jats:italic>n<\/jats:italic>\u2009=\u20099\u201311). Consistent with ASC reductions, bortezomib reduced serum IgM and IgG2a in all mice. Despite these reductions in ASCs and antibody levels, bortezomib did not affect angiotensin II-induced hypertension over 28 days (vehicle: 182\u2009\u00b1\u20094\u2005mmHg vs. bortezomib: 177\u2009\u00b1\u20097\u2005mmHg; <jats:italic>n<\/jats:italic>\u2009=\u20099\u201311).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reductions in ASCs and circulating IgG2a and IgM did not ameliorate experimental hypertension, suggesting other immunoglobulin isotypes or B cell effector functions may promote angiotensin II-induced hypertension.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1184982","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T14:33:24Z","timestamp":1685716404000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Proteasome inhibition reduces plasma cell and antibody secretion, but not angiotensin II-induced 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