TY - JOUR
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 S.
AU - Prasad, Abhiram
AU - Loeffler, Darrell
AU - Lerman, Lilach O.
AU - Khosla, Sundeep
AU - Lerman, Amir
N1 - Funding Information:
The study was supported by the National Institute of Health (NIH, AG004875, AG031750, HL64924, HL085307, DK77013, DK73608, and HL77131) and the Mayo Foundation.
PY - 2010/12
Y1 - 2010/12
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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U2 - 10.1093/eurheartj/ehq373
DO - 10.1093/eurheartj/ehq373
M3 - Article
C2 - 20935001
AN - SCOPUS:78649825728
SN - 0195-668X
VL - 31
SP - 2909
EP - 2914
JO - European heart journal
JF - European heart journal
IS - 23
ER -