C/EBP-β-mediated upregulation of CaV1.2 calcium channel increases arterial constriction in mice with ibrutinib-associated hypertension.

Ibrutinib is linked to hypertension in 225 chronic lymphocytic leukemia (CLL) patients, and in mice it increases arterial constriction via C/EBP-β–driven CaV1.2 upregulation.

• Why it matters: The mechanisms behind ibrutinib-associated hypertension are largely unknown, despite prior links to cardiac calcium dysregulation and the clinical importance of this adverse event.
• What they did: The study followed 225 CLL patients on ibrutinib or watch-and-wait and used mice plus vascular smooth muscle cell experiments to test CaV1.2 regulation by CK2–HSP90β–C/EBP-β.
• The result: In mice, ibrutinib elevated blood pressure and potentiated K+-induced vasoconstriction; C/EBP-β knockdown attenuated CaV1.2 hyperactivity and vasoconstriction, nominating C/EBP-β as a therapeutic target.

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