Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells

Mario Gössl, Ulrike I. Mödder, Rajiv Gulati, Charanjit Rihal, Abhiram Prasad, Darrell Loeffler, Lilach O Lerman, Sundeep Khosla, Amir Lerman

Research output: Contribution to journalArticle

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Abstract

AimsEndothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation. Methods and resultsBlood samples were taken simultaneously from the proximal aorta and the coronary sinus from 31 patients undergoing invasive coronary endothelial function testing. Using flow cytometry, peripheral blood mononuclear cells were analysed for EPC markers (CD133, CD34, KDR) and OCN. The net gradient of EPC was calculated by multiplying the coronary blood flow by the arteriovenous EPC gradient (a negative net gradient indicating retention of EPC). Similarly, serum samples were analysed for stromal cell-derived factor-1 alpha (SDF-1 alpha) and interleukin-8 (IL-8) and their net production calculated. Compared with controls (n = 17) patients with endothelial dysfunction (ED, n = 14) had a significant net retention of CD34+/CD133-/KDR+/ OCN+ EPC [118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00), P = 0.004]. The retention of OCN (+) EPC correlated with the degree of ED. Patients with ED also showed a net retention of CD34+/CD133-/KDR+ EPC (P = 0.010). Net production of IL-8 was positive in ED [1540.80 (-300.40, 21744.10)pg/mL] but negative in controls [-3428.50 (-11225.00, 647.48), P = 0.025]. ConclusionOur study demonstrates that patients with early coronary atherosclerosis are characterized by retention of OCN (+) EPC within the coronary circulation, potentially leading to progressive coronary calcification rather than normal repair.

Original languageEnglish (US)
Pages (from-to)2909-2914
Number of pages6
JournalEuropean Heart Journal
Volume31
Issue number23
DOIs
StatePublished - Dec 2010

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Coronary Artery Disease
Coronary Circulation
Interleukin-8
erucylphosphocholine
Endothelial Progenitor Cells
Chemokine CXCL12
Coronary Sinus
Osteocalcin
Endothelium
Aorta
Blood Cells
Flow Cytometry
Stem Cells
Serum

Keywords

  • Early atherosclerosis
  • Endothelial dysfunction
  • Endothelial progenitor cells
  • Flow cytometry
  • Osteocalcin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells. / Gössl, Mario; Mödder, Ulrike I.; Gulati, Rajiv; Rihal, Charanjit; Prasad, Abhiram; Loeffler, Darrell; Lerman, Lilach O; Khosla, Sundeep; Lerman, Amir.

In: European Heart Journal, Vol. 31, No. 23, 12.2010, p. 2909-2914.

Research output: Contribution to journalArticle

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abstract = "AimsEndothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation. Methods and resultsBlood samples were taken simultaneously from the proximal aorta and the coronary sinus from 31 patients undergoing invasive coronary endothelial function testing. Using flow cytometry, peripheral blood mononuclear cells were analysed for EPC markers (CD133, CD34, KDR) and OCN. The net gradient of EPC was calculated by multiplying the coronary blood flow by the arteriovenous EPC gradient (a negative net gradient indicating retention of EPC). Similarly, serum samples were analysed for stromal cell-derived factor-1 alpha (SDF-1 alpha) and interleukin-8 (IL-8) and their net production calculated. Compared with controls (n = 17) patients with endothelial dysfunction (ED, n = 14) had a significant net retention of CD34+/CD133-/KDR+/ OCN+ EPC [118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00), P = 0.004]. The retention of OCN (+) EPC correlated with the degree of ED. Patients with ED also showed a net retention of CD34+/CD133-/KDR+ EPC (P = 0.010). Net production of IL-8 was positive in ED [1540.80 (-300.40, 21744.10)pg/mL] but negative in controls [-3428.50 (-11225.00, 647.48), P = 0.025]. ConclusionOur study demonstrates that patients with early coronary atherosclerosis are characterized by retention of OCN (+) EPC within the coronary circulation, potentially leading to progressive coronary calcification rather than normal repair.",
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T1 - Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells

AU - Gössl, Mario

AU - Mödder, Ulrike I.

AU - Gulati, Rajiv

AU - Rihal, Charanjit

AU - Prasad, Abhiram

AU - Loeffler, Darrell

AU - Lerman, Lilach O

AU - Khosla, Sundeep

AU - Lerman, Amir

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N2 - AimsEndothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation. Methods and resultsBlood samples were taken simultaneously from the proximal aorta and the coronary sinus from 31 patients undergoing invasive coronary endothelial function testing. Using flow cytometry, peripheral blood mononuclear cells were analysed for EPC markers (CD133, CD34, KDR) and OCN. The net gradient of EPC was calculated by multiplying the coronary blood flow by the arteriovenous EPC gradient (a negative net gradient indicating retention of EPC). Similarly, serum samples were analysed for stromal cell-derived factor-1 alpha (SDF-1 alpha) and interleukin-8 (IL-8) and their net production calculated. Compared with controls (n = 17) patients with endothelial dysfunction (ED, n = 14) had a significant net retention of CD34+/CD133-/KDR+/ OCN+ EPC [118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00), P = 0.004]. The retention of OCN (+) EPC correlated with the degree of ED. Patients with ED also showed a net retention of CD34+/CD133-/KDR+ EPC (P = 0.010). Net production of IL-8 was positive in ED [1540.80 (-300.40, 21744.10)pg/mL] but negative in controls [-3428.50 (-11225.00, 647.48), P = 0.025]. ConclusionOur study demonstrates that patients with early coronary atherosclerosis are characterized by retention of OCN (+) EPC within the coronary circulation, potentially leading to progressive coronary calcification rather than normal repair.

AB - AimsEndothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation. Methods and resultsBlood samples were taken simultaneously from the proximal aorta and the coronary sinus from 31 patients undergoing invasive coronary endothelial function testing. Using flow cytometry, peripheral blood mononuclear cells were analysed for EPC markers (CD133, CD34, KDR) and OCN. The net gradient of EPC was calculated by multiplying the coronary blood flow by the arteriovenous EPC gradient (a negative net gradient indicating retention of EPC). Similarly, serum samples were analysed for stromal cell-derived factor-1 alpha (SDF-1 alpha) and interleukin-8 (IL-8) and their net production calculated. Compared with controls (n = 17) patients with endothelial dysfunction (ED, n = 14) had a significant net retention of CD34+/CD133-/KDR+/ OCN+ EPC [118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00), P = 0.004]. The retention of OCN (+) EPC correlated with the degree of ED. Patients with ED also showed a net retention of CD34+/CD133-/KDR+ EPC (P = 0.010). Net production of IL-8 was positive in ED [1540.80 (-300.40, 21744.10)pg/mL] but negative in controls [-3428.50 (-11225.00, 647.48), P = 0.025]. ConclusionOur study demonstrates that patients with early coronary atherosclerosis are characterized by retention of OCN (+) EPC within the coronary circulation, potentially leading to progressive coronary calcification rather than normal repair.

KW - Early atherosclerosis

KW - Endothelial dysfunction

KW - Endothelial progenitor cells

KW - Flow cytometry

KW - Osteocalcin

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