RATIONALE: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.
RATIONALE: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS:CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.
Authors: Ibhar Al Mheid; Salim S Hayek; Yi-An Ko; Faysal Akbik; Qunna Li; Nima Ghasemzadeh; Greg S Martin; Qi Long; Muhammad Hammadah; A Maziar Zafari; Viola Vaccarino; Edmund K Waller; Arshed A Quyyumi Journal: Circ Res Date: 2016-07-19 Impact factor: 17.367
Authors: Antonio Maria Leone; Sergio Rutella; Giuseppina Bonanno; Anna Maria Contemi; Daniela G de Ritis; Maria Benedetta Giannico; Antonio G Rebuzzi; Giuseppe Leone; Filippo Crea Journal: Int J Cardiol Date: 2005-07-26 Impact factor: 4.164
Authors: M Peichev; A J Naiyer; D Pereira; Z Zhu; W J Lane; M Williams; M C Oz; D J Hicklin; L Witte; M A Moore; S Rafii Journal: Blood Date: 2000-02-01 Impact factor: 22.113
Authors: U M Gehling; S Ergün; U Schumacher; C Wagener; K Pantel; M Otte; G Schuch; P Schafhausen; T Mende; N Kilic; K Kluge; B Schäfer; D K Hossfeld; W Fiedler Journal: Blood Date: 2000-05-15 Impact factor: 22.113
Authors: S Shintani; T Murohara; H Ikeda; T Ueno; T Honma; A Katoh; K Sasaki; T Shimada; Y Oike; T Imaizumi Journal: Circulation Date: 2001-06-12 Impact factor: 29.690
Authors: Christopher R Cogle; Elizabeth Wise; Amy M Meacham; Claudia Zierold; Jay H Traverse; Timothy D Henry; Emerson C Perin; James T Willerson; Stephen G Ellis; Marjorie Carlson; David X M Zhao; Roberto Bolli; John P Cooke; Saif Anwaruddin; Aruni Bhatnagar; Maria da Graca Cabreira-Hansen; Maria B Grant; Dejian Lai; Lem Moyé; Ray F Ebert; Rachel E Olson; Shelly L Sayre; Ivonne H Schulman; Raphael C Bosse; Edward W Scott; Robert D Simari; Carl J Pepine; Doris A Taylor Journal: Circ Res Date: 2014-08-18 Impact factor: 17.367
Authors: D Orlic; J Kajstura; S Chimenti; F Limana; I Jakoniuk; F Quaini; B Nadal-Ginard; D M Bodine; A Leri; P Anversa Journal: Proc Natl Acad Sci U S A Date: 2001-08-14 Impact factor: 11.205
Authors: Daniel J Ceradini; Anita R Kulkarni; Matthew J Callaghan; Oren M Tepper; Nicholas Bastidas; Mark E Kleinman; Jennifer M Capla; Robert D Galiano; Jamie P Levine; Geoffrey C Gurtner Journal: Nat Med Date: 2004-07-04 Impact factor: 53.440
Authors: Shabatun J Islam; Jeong Hwan Kim; Matthew Topel; Chang Liu; Yi-An Ko; Mahasin S Mujahid; Mario Sims; Mohamed Mubasher; Kiran Ejaz; Jan Morgan-Billingslea; Kia Jones; Edmund K Waller; Dean Jones; Karan Uppal; Sandra B Dunbar; Priscilla Pemu; Viola Vaccarino; Charles D Searles; Peter Baltrus; Tené T Lewis; Arshed A Quyyumi; Herman Taylor Journal: J Am Heart Assoc Date: 2020-04-28 Impact factor: 5.501
Authors: Mariola Olkowicz; Izabela Czyzynska-Cichon; Natalia Szupryczynska; Renata B Kostogrys; Zdzislaw Kochan; Janusz Debski; Michal Dadlez; Stefan Chlopicki; Ryszard T Smolenski Journal: J Transl Med Date: 2021-01-06 Impact factor: 5.531