Regulation of circulating progenitor cells in left ventricular dysfunction.

Barry A. Boilson, Katarina Larsen, Adriana Harbuzariu, Sinny Delacroix, Josef Korinek, Harald Froehlich, Kent R Bailey, Christopher G. Scott, Brian P Shapiro, Guido Boerrigter, Horng Haur Chen, Margaret May Redfield, John C Jr. Burnett, Robert D. Simari

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

Original languageEnglish (US)
Pages (from-to)635-642
Number of pages8
JournalCirculation. Heart failure
Volume3
Issue number5
DOIs
StatePublished - Sep 1 2010

Fingerprint

Left Ventricular Dysfunction
Stem Cells
Desoxycorticosterone
Mineralocorticoids
Acetates
Dogs
Kidney
Telomerase
Aldosterone
Canidae
Cardiovascular Diseases
Bone Marrow
Phenotype
Survival
erucylphosphocholine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Boilson, B. A., Larsen, K., Harbuzariu, A., Delacroix, S., Korinek, J., Froehlich, H., ... Simari, R. D. (2010). Regulation of circulating progenitor cells in left ventricular dysfunction. Circulation. Heart failure, 3(5), 635-642. https://doi.org/10.1161/CIRCHEARTFAILURE.109.879437

Regulation of circulating progenitor cells in left ventricular dysfunction. / Boilson, Barry A.; Larsen, Katarina; Harbuzariu, Adriana; Delacroix, Sinny; Korinek, Josef; Froehlich, Harald; Bailey, Kent R; Scott, Christopher G.; Shapiro, Brian P; Boerrigter, Guido; Chen, Horng Haur; Redfield, Margaret May; Burnett, John C Jr.; Simari, Robert D.

In: Circulation. Heart failure, Vol. 3, No. 5, 01.09.2010, p. 635-642.

Research output: Contribution to journalArticle

Boilson, BA, Larsen, K, Harbuzariu, A, Delacroix, S, Korinek, J, Froehlich, H, Bailey, KR, Scott, CG, Shapiro, BP, Boerrigter, G, Chen, HH, Redfield, MM, Burnett, JCJ & Simari, RD 2010, 'Regulation of circulating progenitor cells in left ventricular dysfunction.', Circulation. Heart failure, vol. 3, no. 5, pp. 635-642. https://doi.org/10.1161/CIRCHEARTFAILURE.109.879437
Boilson BA, Larsen K, Harbuzariu A, Delacroix S, Korinek J, Froehlich H et al. Regulation of circulating progenitor cells in left ventricular dysfunction. Circulation. Heart failure. 2010 Sep 1;3(5):635-642. https://doi.org/10.1161/CIRCHEARTFAILURE.109.879437
Boilson, Barry A. ; Larsen, Katarina ; Harbuzariu, Adriana ; Delacroix, Sinny ; Korinek, Josef ; Froehlich, Harald ; Bailey, Kent R ; Scott, Christopher G. ; Shapiro, Brian P ; Boerrigter, Guido ; Chen, Horng Haur ; Redfield, Margaret May ; Burnett, John C Jr. ; Simari, Robert D. / Regulation of circulating progenitor cells in left ventricular dysfunction. In: Circulation. Heart failure. 2010 ; Vol. 3, No. 5. pp. 635-642.
@article{261a19827ce84182a3700832f8f041e1,
title = "Regulation of circulating progenitor cells in left ventricular dysfunction.",
abstract = "BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.",
author = "Boilson, {Barry A.} and Katarina Larsen and Adriana Harbuzariu and Sinny Delacroix and Josef Korinek and Harald Froehlich and Bailey, {Kent R} and Scott, {Christopher G.} and Shapiro, {Brian P} and Guido Boerrigter and Chen, {Horng Haur} and Redfield, {Margaret May} and Burnett, {John C Jr.} and Simari, {Robert D.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1161/CIRCHEARTFAILURE.109.879437",
language = "English (US)",
volume = "3",
pages = "635--642",
journal = "Circulation: Heart Failure",
issn = "1941-3297",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Regulation of circulating progenitor cells in left ventricular dysfunction.

AU - Boilson, Barry A.

AU - Larsen, Katarina

AU - Harbuzariu, Adriana

AU - Delacroix, Sinny

AU - Korinek, Josef

AU - Froehlich, Harald

AU - Bailey, Kent R

AU - Scott, Christopher G.

AU - Shapiro, Brian P

AU - Boerrigter, Guido

AU - Chen, Horng Haur

AU - Redfield, Margaret May

AU - Burnett, John C Jr.

AU - Simari, Robert D.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

AB - BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

UR - http://www.scopus.com/inward/record.url?scp=77957917252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957917252&partnerID=8YFLogxK

U2 - 10.1161/CIRCHEARTFAILURE.109.879437

DO - 10.1161/CIRCHEARTFAILURE.109.879437

M3 - Article

C2 - 20573992

AN - SCOPUS:77957917252

VL - 3

SP - 635

EP - 642

JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

SN - 1941-3297

IS - 5

ER -