CXCR4+ and FLK-1+ identify circulating cells associated with improved cardiac function in patients following myocardial infarction

Rahul Suresh; Anca Chiriac; Kashish Goel; Hector R. Villarraga; Francisco Lopez-Jimenez; Randal J. Thomas; Andre Terzic; Timothy J. Nelson; Carmen Perez-Terzic

doi:10.1007/s12265-013-9502-z

CXCR4⁺ and FLK-1⁺ identify circulating cells associated with improved cardiac function in patients following myocardial infarction

Rahul Suresh
, Anca Chiriac
, Kashish Goel
, Hector R. Villarraga
, Francisco Lopez-Jimenez
, Randal J. Thomas
, Andre Terzic
, Timothy J. Nelson
, Carmen Perez-Terzic

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

The biomarkers CXCR4/FLK-1 select cardiac progenitors from a stem cell pool in experimental models. However, the translational value of these cells in human ischemic heart disease is unknown. Here, flow-cytometry identified CD45^-/CXCR4⁺/FLK-1⁺ cells in 30 individuals without ischemic heart disease and 33 first-time acute myocardial infarction (AMI) patients. AMI patients had higher CD45^-/CXCR4 ⁺/FLK-1⁺ cell-load at 48-h and 3- and 6-months post-AMI (p = 0.003,0.04,0.04, respectively) than controls. Cardiovascular risk factors and left ventricular (LV) ejection fraction were not associated with cell-load. 2D-speckle-tracking strain echocardiography assessment of LV systolic function showed improvement in longitudinal strain and dyssynchrony during follow-up associated with longitudinal increases in and higher 48-h post-AMI CD45 ^-/CXCR4⁺/FLK-1⁺ cell-load (r = -0.525, p = 0.025; r = -0.457, p = 0.029, respectively). In conclusion, CD45 ^-/CXCR4⁺/FLK-1⁺ cells are present in adult human circulation, increased in AMI and associated with improved LV systolic function. Thus, CD45^-/CXCR4⁺/FLK-1⁺ cells may provide a diagnostic tool to follow cardiac regenerative capacity and potentially serve as a prognostic marker in AMI.

Original language	English (US)
Pages (from-to)	787-797
Number of pages	11
Journal	Journal of cardiovascular translational research
Volume	6
Issue number	5
DOIs	https://doi.org/10.1007/s12265-013-9502-z
State	Published - Oct 2013

Keywords

CXCR4
Cardiac progenitor cells
FLK-1
Longitudinal strain
Myocardial infarction

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmaceutical Science
Cardiology and Cardiovascular Medicine
Genetics(clinical)

Access to Document

10.1007/s12265-013-9502-z

Cite this

Suresh, R., Chiriac, A., Goel, K., Villarraga, H. R., Lopez-Jimenez, F., Thomas, R. J., Terzic, A., Nelson, T. J., & Perez-Terzic, C. (2013). CXCR4⁺ and FLK-1⁺ identify circulating cells associated with improved cardiac function in patients following myocardial infarction. Journal of cardiovascular translational research, 6(5), 787-797. https://doi.org/10.1007/s12265-013-9502-z

Suresh, R, Chiriac, A, Goel, K, Villarraga, HR , Lopez-Jimenez, F, Thomas, RJ, Terzic, A , Nelson, TJ & Perez-Terzic, C 2013, 'CXCR4⁺ and FLK-1⁺ identify circulating cells associated with improved cardiac function in patients following myocardial infarction', Journal of cardiovascular translational research, vol. 6, no. 5, pp. 787-797. https://doi.org/10.1007/s12265-013-9502-z

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title = "CXCR4+ and FLK-1+ identify circulating cells associated with improved cardiac function in patients following myocardial infarction",

abstract = "The biomarkers CXCR4/FLK-1 select cardiac progenitors from a stem cell pool in experimental models. However, the translational value of these cells in human ischemic heart disease is unknown. Here, flow-cytometry identified CD45-/CXCR4+/FLK-1+ cells in 30 individuals without ischemic heart disease and 33 first-time acute myocardial infarction (AMI) patients. AMI patients had higher CD45-/CXCR4 +/FLK-1+ cell-load at 48-h and 3- and 6-months post-AMI (p = 0.003,0.04,0.04, respectively) than controls. Cardiovascular risk factors and left ventricular (LV) ejection fraction were not associated with cell-load. 2D-speckle-tracking strain echocardiography assessment of LV systolic function showed improvement in longitudinal strain and dyssynchrony during follow-up associated with longitudinal increases in and higher 48-h post-AMI CD45 -/CXCR4+/FLK-1+ cell-load (r = -0.525, p = 0.025; r = -0.457, p = 0.029, respectively). In conclusion, CD45 -/CXCR4+/FLK-1+ cells are present in adult human circulation, increased in AMI and associated with improved LV systolic function. Thus, CD45-/CXCR4+/FLK-1+ cells may provide a diagnostic tool to follow cardiac regenerative capacity and potentially serve as a prognostic marker in AMI.",

keywords = "CXCR4, Cardiac progenitor cells, FLK-1, Longitudinal strain, Myocardial infarction",

author = "Rahul Suresh and Anca Chiriac and Kashish Goel and Villarraga, \{Hector R.\} and Francisco Lopez-Jimenez and Thomas, \{Randal J.\} and Andre Terzic and Nelson, \{Timothy J.\} and Carmen Perez-Terzic",

note = "Funding Information: Funding This work was supported in part by the Todd and Karen Wanek Program for Hypoplastic Left Heart Syndrome, Marriott Regenerative Medicine Award, and Mayo Clinic. It was also supported by CTSA Grant Number UL1 TR000135 and TL1 TR000137 from the National Center for Advancing Translational Science (NCATS).",

year = "2013",

month = oct,

doi = "10.1007/s12265-013-9502-z",

language = "English (US)",

volume = "6",

pages = "787--797",

journal = "Journal of cardiovascular translational research",

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T1 - CXCR4+ and FLK-1+ identify circulating cells associated with improved cardiac function in patients following myocardial infarction

AU - Suresh, Rahul

AU - Chiriac, Anca

AU - Goel, Kashish

AU - Villarraga, Hector R.

AU - Lopez-Jimenez, Francisco

AU - Thomas, Randal J.

AU - Terzic, Andre

AU - Nelson, Timothy J.

AU - Perez-Terzic, Carmen

N1 - Funding Information: Funding This work was supported in part by the Todd and Karen Wanek Program for Hypoplastic Left Heart Syndrome, Marriott Regenerative Medicine Award, and Mayo Clinic. It was also supported by CTSA Grant Number UL1 TR000135 and TL1 TR000137 from the National Center for Advancing Translational Science (NCATS).

PY - 2013/10

Y1 - 2013/10

N2 - The biomarkers CXCR4/FLK-1 select cardiac progenitors from a stem cell pool in experimental models. However, the translational value of these cells in human ischemic heart disease is unknown. Here, flow-cytometry identified CD45-/CXCR4+/FLK-1+ cells in 30 individuals without ischemic heart disease and 33 first-time acute myocardial infarction (AMI) patients. AMI patients had higher CD45-/CXCR4 +/FLK-1+ cell-load at 48-h and 3- and 6-months post-AMI (p = 0.003,0.04,0.04, respectively) than controls. Cardiovascular risk factors and left ventricular (LV) ejection fraction were not associated with cell-load. 2D-speckle-tracking strain echocardiography assessment of LV systolic function showed improvement in longitudinal strain and dyssynchrony during follow-up associated with longitudinal increases in and higher 48-h post-AMI CD45 -/CXCR4+/FLK-1+ cell-load (r = -0.525, p = 0.025; r = -0.457, p = 0.029, respectively). In conclusion, CD45 -/CXCR4+/FLK-1+ cells are present in adult human circulation, increased in AMI and associated with improved LV systolic function. Thus, CD45-/CXCR4+/FLK-1+ cells may provide a diagnostic tool to follow cardiac regenerative capacity and potentially serve as a prognostic marker in AMI.

AB - The biomarkers CXCR4/FLK-1 select cardiac progenitors from a stem cell pool in experimental models. However, the translational value of these cells in human ischemic heart disease is unknown. Here, flow-cytometry identified CD45-/CXCR4+/FLK-1+ cells in 30 individuals without ischemic heart disease and 33 first-time acute myocardial infarction (AMI) patients. AMI patients had higher CD45-/CXCR4 +/FLK-1+ cell-load at 48-h and 3- and 6-months post-AMI (p = 0.003,0.04,0.04, respectively) than controls. Cardiovascular risk factors and left ventricular (LV) ejection fraction were not associated with cell-load. 2D-speckle-tracking strain echocardiography assessment of LV systolic function showed improvement in longitudinal strain and dyssynchrony during follow-up associated with longitudinal increases in and higher 48-h post-AMI CD45 -/CXCR4+/FLK-1+ cell-load (r = -0.525, p = 0.025; r = -0.457, p = 0.029, respectively). In conclusion, CD45 -/CXCR4+/FLK-1+ cells are present in adult human circulation, increased in AMI and associated with improved LV systolic function. Thus, CD45-/CXCR4+/FLK-1+ cells may provide a diagnostic tool to follow cardiac regenerative capacity and potentially serve as a prognostic marker in AMI.

KW - CXCR4

KW - Cardiac progenitor cells

KW - FLK-1

KW - Longitudinal strain

KW - Myocardial infarction

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DO - 10.1007/s12265-013-9502-z

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