Abstract 19078: Adipose-derived Cell Treatment Improves Coronary Blood Flow Reserve in Aged Females and is Associated With Altered ROS Production in Coronary Arterioles
Coronary blood flow reserve (CFR) is significantly decreased with advancing age and could contribute simultaneously to the increased risk for coronary heart disease (CHD). CFR is now considered a novel diagnostic tool for CHD, especially in older women among whom dysfunctional CFR is most prevalent. Adipose-derived stromal vascular fraction (SVF) cells have shown an innate capacity for angiogenesis and regeneration in the periphery and are being used in numerous clinical trials. We wanted to assess the therapeutic potential of SVF to improve poor CFR in aged female rats and evaluate vascular reactivity and ROS signaling mechanisms in isolated epicardial coronary arterioles.
SVF was isolated from adipose tissue of female rats through mincing, enzymatic digestion, and removal of buoyant adipocytes. SVF (1x10(6) cells/cm2) was plated on Vicryl® and cultured for 14 days before implantation on epicardial surface of old F344 rats (22 mos). After 6 weeks, microspheres were injected during baseline and dobutamine infusion to evaluate CFR (hyperemic BF/ baseline BF). Coronary arterioles were isolated, pressurized and vascular reactivity and ROS production to increasing levels of shear stress was assessed.
CFR in the apical region of the LV was increased by 78+/-10% following treatment with a SVF epicardial patch, while the papillary region was increased by 28+/-12% compared to untreated hearts from aged animals (n=8, SVF; n=5, Control). Flow-dependent vasodilation in isolated arterioles was improved in hearts treated with SVF (5-25 ul/min). This increase in vascular reactivity after SVF treatment was associated with decreased NO but increased H2O2 production during 20 ul/min intraluminal flow, as measured by ROS-specific dyes (DAF and DCF, respectively).
These results suggest that this adipose-derived cell-based therapy could reverse age-related declines in the reactivity of the coronary microvasculature through ROS-related mechanisms. Specifically, a conversion from NO- to H2O2 -dependent vasodilation may be mediating the improved flow-induced vasodilation in old female hearts treated with SVF. More studies need to be performed to determine specific SVF cell involvement, duration of improvement and efficacy of alternative cell delivery protocols.
- Coronary microcirculation
- Regenerative medicine stem cells
- Reactive oxygen intermediates
- Blood flow
Author Disclosures: C.D. Nevitt: None. A.L. Aird: None. Q.T. Nguyen: None. J.B. Hoying: None. S.K. Williams: None. A. LeBlanc: Ownership Interest; Modest; Patent-pending and license option agreement for "Adipose Stromal Vascular Fraction Cell Epicardial Patch" with Tissue Genesis.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.