Enhanced Beta-1 Adrenergic Receptor Responsiveness in Coronary Arterioles Following Intravenous Stromal Vascular Fraction Therapy in Aged Rats

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2019 Jul 13

PMID 31296794

Citations 9

Authors

Gabrielle Rowe

Natia Q Kelm

Jason E Beare

Evan Tracy

Fangping Yuan

Amanda J LeBlanc

Affiliations

Soon will be listed here.

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: 1x10 green fluorescent protein (GFP+) SVF cells (O+SVF, n=21), and 5x10 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.

Citing Articles

Therapeutic application of adipose-derived stromal vascular fraction in myocardial infarction.

Gareev I, Beylerli O, Ilyasova T, Ahmad A, Shi H, Chekhonin V iScience. 2024; 27(5):109791.

PMID: 38736548 PMC: 11088339. DOI: 10.1016/j.isci.2024.109791.

Stromal Vascular Fraction Reverses the Age-Related Impairment in Revascularization following Injury.

Rowe G, Heng D, Beare J, Hodges N, Tracy E, Murfee W J Vasc Res. 2022; 59(6):343-357.

PMID: 36075199 PMC: 9780192. DOI: 10.1159/000526002.

Adipose stromal vascular fraction reverses mitochondrial dysfunction and hyperfission in aging-induced coronary microvascular disease.

Tracy E, Nair R, Rowe G, Beare J, Beyer A, LeBlanc A Am J Physiol Heart Circ Physiol. 2022; 323(4):H749-H762.

PMID: 36018760 PMC: 9529257. DOI: 10.1152/ajpheart.00311.2022.

Stromal Vascular Fraction Restores Vasodilatory Function by Reducing Oxidative Stress in Aging-Induced Coronary Microvascular Disease.

Tracy E, Dukes M, Rowe G, Beare J, Nair R, LeBlanc A Antioxid Redox Signal. 2022; 38(4-6):261-281.

PMID: 35950616 PMC: 9968627. DOI: 10.1089/ars.2021.0249.

Cell therapy-induced recovery of dysfunctional microvasculature.

Tracy E, Rowe G, LeBlanc A Aging (Albany NY). 2022; 14(13):5296-5298.

PMID: 35832022 PMC: 9320541. DOI: 10.18632/aging.204183.

References

Hachamovitch R, Wicker P, Capasso J, Anversa P . Alterations of coronary blood flow and reserve with aging in Fischer 344 rats. Am J Physiol. 1989; 256(1 Pt 2):H66-73. DOI: 10.1152/ajpheart.1989.256.1.H66. View

Lennon D, Haynesworth S, Young R, Dennis J, Caplan A . A chemically defined medium supports in vitro proliferation and maintains the osteochondral potential of rat marrow-derived mesenchymal stem cells. Exp Cell Res. 1995; 219(1):211-22. DOI: 10.1006/excr.1995.1221. View

Stolzing A, Jones E, McGonagle D, Scutt A . Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008; 129(3):163-73. DOI: 10.1016/j.mad.2007.12.002. View

Collins S, Cao W, Robidoux J . Learning new tricks from old dogs: beta-adrenergic receptors teach new lessons on firing up adipose tissue metabolism. Mol Endocrinol. 2004; 18(9):2123-31. DOI: 10.1210/me.2004-0193. View

Sheu J, Lee M, Wallace C, Chen K, Sung P, Chua S . Therapeutic effects of adipose derived fresh stromal vascular fraction-containing stem cells versus cultured adipose derived mesenchymal stem cells on rescuing heart function in rat after acute myocardial infarction. Am J Transl Res. 2019; 11(1):67-86. PMC: 6357301. View

Abdelkrim M, Leonetti D, Montaudon E, Chatagnon G, Gogny M, Desfontis J . Antibodies against the second extracellular loop of β₁-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat. Int Immunopharmacol. 2014; 19(2):308-16. DOI: 10.1016/j.intimp.2014.01.029. View

Brodde O, Khamssi M, Zerkowski H . Beta-adrenoceptors in the transplanted human heart: unaltered beta-adrenoceptor density, but increased proportion of beta 2-adrenoceptors with increasing posttransplant time. Naunyn Schmiedebergs Arch Pharmacol. 1991; 344(4):430-6. DOI: 10.1007/BF00172582. View

Zakhari J, Zabonick J, Gettler B, Williams S . Vasculogenic and angiogenic potential of adipose stromal vascular fraction cell populations in vitro. In Vitro Cell Dev Biol Anim. 2017; 54(1):32-40. PMC: 5760587. DOI: 10.1007/s11626-017-0213-7. View

Lefkowitz R, Pitcher J, Krueger K, Daaka Y . Mechanisms of beta-adrenergic receptor desensitization and resensitization. Adv Pharmacol. 1997; 42:416-20. DOI: 10.1016/s1054-3589(08)60777-2. View

10.

Mendzef S, Slovinski J . Neurohormones and heart failure. Nurs Clin North Am. 2004; 39(4):845-61. DOI: 10.1016/j.cnur.2004.07.004. View

11.

Kelm N, Beare J, LeBlanc A . Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats. J Vis Exp. 2019; (148). PMC: 6996202. DOI: 10.3791/59406. View

12.

Schutzer W, Mader S . Age-related changes in vascular adrenergic signaling: clinical and mechanistic implications. Ageing Res Rev. 2003; 2(2):169-90. DOI: 10.1016/s1568-1637(02)00063-6. View

13.

Sun D, Huang A, Mital S, Kichuk M, Marboe C, Addonizio L . Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles. Circulation. 2002; 106(5):550-5. DOI: 10.1161/01.cir.0000023896.70583.9f. View

14.

Chilian W, Eastham C, Marcus M . Microvascular distribution of coronary vascular resistance in beating left ventricle. Am J Physiol. 1986; 251(4 Pt 2):H779-88. DOI: 10.1152/ajpheart.1986.251.4.H779. View

15.

Engelhardt S, Bohm M, Erdmann E, Lohse M . Analysis of beta-adrenergic receptor mRNA levels in human ventricular biopsy specimens by quantitative polymerase chain reactions: progressive reduction of beta 1-adrenergic receptor mRNA in heart failure. J Am Coll Cardiol. 1996; 27(1):146-54. DOI: 10.1016/0735-1097(95)00425-4. View

16.

Besedovsky H, Del Rey A . Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev. 1996; 17(1):64-102. DOI: 10.1210/edrv-17-1-64. View

17.

Liggett S . Update on current concepts of the molecular basis of beta2-adrenergic receptor signaling. J Allergy Clin Immunol. 2002; 110(6 Suppl):S223-7. DOI: 10.1067/mai.2002.129945. View

18.

Pepine C, Anderson R, Sharaf B, Reis S, Smith K, Handberg E . Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010; 55(25):2825-32. PMC: 2898523. DOI: 10.1016/j.jacc.2010.01.054. View

19.

Lee J, Lee S, Youn Y, Ahn M, Kim J, Yoo B . A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction. J Korean Med Sci. 2014; 29(1):23-31. PMC: 3890472. DOI: 10.3346/jkms.2014.29.1.23. View

20.

Brodde O, Michel M, Zerkowski H . Signal transduction mechanisms controlling cardiac contractility and their alterations in chronic heart failure. Cardiovasc Res. 1995; 30(4):570-84. View