Abstract 17741: Blood Pressure Homeostasis Depends on Normal c-myb Activity in Bone Marrow-derived Cells
Background: We have shown that the proto-oncogene c-myb regulates the proliferation and differentiation of vascular smooth muscle cells (VSMCs). The role of c-Myb in baseline cardiovascular function has eluded examination due to the embryonic lethality of c-myb-/- mice. We have obtained a mouse line that harbours an ENU-generated point mutation in c-myb, resulting in a hypomorphic c-myb (h) allele with compromised c-Myb activity.
Objective: To compare and contrast the cardiovascular pathophysiology of mice homozygous for the hypomorphic c-myb (c-mybh/h) with wild-type mice (c-mybwt)
Methods & Results: Invasive hemodynamics were performed on 12-week old male c-mybh/h and c-mybwt mice under isoflurane anaesthesia using a Millar pressure-transducing catheter introduced via the right common carotid artery. c-mybh/h mice (n = 14) showed decreased aortic systolic blood pressure (BP) (103.6±2.3 vs. 120.2±1.1 mmHg; p<0.0001) and aortic diastolic BP (70.9±2.3 vs. 83.2±1.3 mmHg; p<0.001) compared to c-mybwt (n = 14). No differences were found using echocardiography. Radiotelemetry revealed that differences in BP persisted in unanesthesized animals. To determine if lower BP was due to defects in VSMC contractility, perfusion myographic analysis of mesenteric arteries was performed, but no differences in contractile function were found. To determine if low blood pressure in c-mybh/h mice is due to defects in vessel, cardiac or bone marrow (BM)-derived cells, we performed BM transplantation of c-mybwt or c-mybh/h BM into c-mybh/h mice. Invasive hemodynamics on 12-week old male c-mybwt→h/h and c-mybh/h→h/h mice revealed that c-mybwt BM restored normal aortic systolic blood pressure in c-mybh/h recipient mice (118.7±1.5 vs. 106.8±2.9 mmHg; n=9&6; p=0.05). When challenged with DOCA-salt hypertension, c-mybh/h mice had lower blood pressure versus c-mybwt mice (132.8±6.5 vs. 152.4±5.5 mmHg; n=7/group; p<0.05).
Conclusions: The low blood pressure of c-mybh/h mice is due to defective c-myb activity in BM-derived cell populations. c-mybh/h mice are also protected from hypertension. Together, these data suggest that specific cell populations derived from BM known to be involved in blood pressure homeostasis may critically depend on normal c-myb activity.
- © 2013 by American Heart Association, Inc.