Abstract 16694: Transplantation of Bone Marrow Cells From miR150 Knockout Mice Attenuates Arterial Stiffness and Hypertension in Senescence-accelerated Mice P1 (SAMP1)
Background & Objective. Aging is associated with increased prevalence of arterial stiffness and hypertension. The senescence-accelerated mouse P1 (SAMP1) demonstrates early and spontaneous aging phenotypes around 6-8 months of age. In contrast, microRNA-150 knockout (miR15-KO) slows down the aging process and extends lifespan in mice by 20-30%. The objective of this study is to investigate if arterial stiffness and hypertension occur in SAMP1 mice and if transplantation of bone marrow cells (BMCs) from miR-150 KO mice affects arterial stiffening and hypertension in SAMP1 mice.
Method & Results. The results showed that blood pressure (BP) and pulse wave velocity (PWV) were increased significantly in the SAMP1 mice vs. the age-matched control (AKR/J) mice (10 months). Therefore, SAMP1 mice developed arterial stiffening and hypertension. Western blot analysis showed that collagen 1 and TGFβ1 expression were increased but the elastin expression was decreased in aortas of SAMP1 mice, indicating arterial remodeling. Klotho is a recently-discovered aging-suppressor gene. Plasma levels klotho protein and renal expression of klotho protein were decreased in SAMP1 mice. Interestingly, transplantation of BMCs from miR150-KO mice decreased PWV and BP in SAMP1 mice to nearly control levels within 3 months, suggesting that BMC transplantation attenuates senescence-related arterial stiffening and hypertension. BMC transplantation from miR150-KO mice increased plasma levels of klotho and renal expression of klotho and abolished T cell and macrophage infiltration in aortas and kidneys in SAMP1 mice. BMC transplantation decreased expression of collagen 1 and TGFβ1 but increased expression of elastin in aortas in SAMP1 mice.
Conclusion. Accelerated aging led to arterial stiffness and hypertension in SAMP1 mice. BMC transplantation from miR150-KO mice reversed arterial stiffness and hypertension in SAMP1 mice. This study demonstrates, for the first time, that BMC transplantation may be an effective therapeutic approach for aging-related arterial stiffness and hypertension. (supported by NIH R01 HL105302 & HL102074).
Author Disclosures: J. Fan: None. S. Wang: None. Z. Sun: None.
- © 2015 by American Heart Association, Inc.