B-Cell Deficiency Lowers Blood Pressure in Mice
| Autor: | Filio Billia, Felix Chiu, Craig A. Simmons, Rickvinder Besla, Abdul Momen, Danny D. Dinh, Clinton S. Robbins, Luke S. Dingwell, Scott P. Heximer, Eric A. Shikatani, Rohan John, Jennifer L. Gommerman, Mansoor Husain, Talat Afroze, James W. Scholey, Steffen-Sebastian Bolz, Hangjun Zhang, Michelle B. Chen, Andrew S. Levy |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Vascular smooth muscle Myocytes Smooth Muscle Blood Pressure B-Cell Deficiency 030204 cardiovascular system & hematology Mice Proto-Oncogene Proteins c-myb 03 medical and health sciences 0302 clinical medicine Internal medicine Internal Medicine medicine Animals Transcription factor Mice Knockout B-Lymphocytes Kidney Chemistry Cell Differentiation Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Blood pressure medicine.anatomical_structure Gene Expression Regulation Hypertension RNA |
| Zdroj: | Hypertension. 73:561-570 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.118.11828 |
| Popis: | The proto-oncogene c-myb (and corresponding nuclear transcription factor, c-Myb) regulates the proliferation and differentiation of hematologic and vascular smooth muscle cells; however, the role of c-Myb in blood pressure regulation is unknown. Here, we show that mice homozygous for a hypomorphic c-myb allele ( c-myb h/h ) conferring reduced c-Myb activity manifest reduced peripheral blood and kidney B220 + B-cells and have decreased systolic (104±2 versus 120±1 mm Hg; P P WT (wild type) mice. Additionally, c-myb h/h mice had lower susceptibility to deoxycorticosterone acetate-salt experimental hypertension. Although cardiac (echocardiography) and resistance artery (perfusion myography) functions were normal, metabolic cage studies revealed that c-myb h/h mice had increased 24-hour urine output and sodium excretion versus WT . Reconstitution of WT mice with c-myb h/h bone marrow transplant and chimeric bone marrow transplant using mice lacking B-cells ( J H T ; h/h>WT and h/h:J H T>WT , respectively) decreased blood pressure and increased 24-hour urine output compared with controls ( WT>WT ; WT:J H T>WT ). J H T mice also had decreased systolic (103±2 versus 115±1 mm Hg; P P WT . Real-time quantitative reverse transcription polymerase chain reaction of kidney medulla revealed reduced V 2 R (vasopressin receptor 2) expression in c-myb h/h and J H T mice. These data implicate B-cells in the regulation of V 2 R and its associated effects on salt and water handling and blood pressure homeostasis. |
| Databáze: | OpenAIRE |
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