Research Paper Volume 11, Issue 13 pp 4561—4578

Enhanced beta-1 adrenergic receptor responsiveness in coronary arterioles following intravenous stromal vascular fraction therapy in aged rats

Gabrielle Rowe 1, 2, , Natia Q. Kelm 1, , Jason E. Beare 1, 3, , Evan Tracy 1, 2, , Fangping Yuan 1, , Amanda J. LeBlanc 1, 2, ,

  • 1 Cardiovascular Innovation Institute, University of Louisville, Louisville, KY 40292, USA
  • 2 Department of Physiology, University of Louisville, Louisville, KY 40292, USA
  • 3 Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40292, USA

received: May 15, 2019 ; accepted: June 25, 2019 ; published: July 11, 2019 ;

https://doi.org/10.18632/aging.102069
How to Cite

Copyright: Rowe et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Our past study showed that a single tail vein injection of adipose-derived stromal vascular fraction (SVF) into old rats was associated with improved dobutamine-mediated coronary flow reserve. We hypothesize that i.v. injection of SVF improves coronary microvascular function in aged rats via alterations in beta adrenergic microvascular signaling. Female Fischer-344 rats aged young (3 months, n=32) and old (24 months, n=30) were utilized, along with two cell therapies intravenously injected in old rats four weeks prior to sacrifice: 1x107 green fluorescent protein (GFP+) SVF cells (O+SVF, n=21), and 5x106 GFP+ bone-marrow mesenchymal stromal cells (O+BM, n=6), both harvested from young donors. Cardiac ultrasound and pressure-volume measurements were obtained, and coronary arterioles were isolated from each group for microvessel reactivity studies and immunofluorescence staining. Coronary flow reserve decreased with advancing age, but this effect was rescued by the SVF treatment in the O+SVF group. Echocardiography showed an age-related diastolic dysfunction that was improved with SVF to a greater extent than with BM treatment. Coronary arterioles isolated from SVF-treated rats showed amelioration of the age-related decrease in vasodilation to a non-selective β-AR agonist. I.v. injected SVF cells improved β-adrenergic receptor-dependent coronary flow and microvascular function in a model of advanced age.

Abbreviations

β-AR: beta-adrenergic receptor; 5HT: serotonin; AC: adenylyl cyclase; BF: blood flow; BM-MSC: bone marrow-mesenchymal stem cell; BW: body weight; CFR: coronary flow reserve; CMD: coronary microvascular disease; CO: cardiac output; CVD: cardiovascular disease; DA: dopamine; EF: ejection fraction; EPI: epinephrine; FS: fractional shortening; Gαi: inhibitory G protein; Gαs: stimulatory G protein; GFP+: green fluorescent protein; HF: heart failure; i.v.: intravenous; IVC: inferior vena cava; IVRT: isovolumic relaxation time; LAD: left anterior descending; LV: left ventricle; LVDP: left ventricular diastolic pressure; LVDs/d: left ventricular dimensions systolic/diastolic; LVVs/d: left ventricular volume systolic/diastolic; MI: myocardial infarction; MSC: mesenchymal stem/stromal cells; NE: norepinephrine; NO: nitric oxide; O+BM: old injected with GFP+ bone marrow-mesenchymal stem cells; O+SVF: old injected with GFP+ adipose-derived stromal vascular fraction cells; OC: old control; PRSW: preload recruitable stroke work; PV: pressure-volume; ROI: regions of interest; RT: room temperature; SV: stroke volume; SVF: adipose-derived stromal vascular fraction; VSMC: vascular smooth muscle cell; YC: young control.