RATIONALE: We investigated aging of human endogenous reparative capacity and aimed to clarify whether it is affected by presence of cardiovascular disease or its risk factors (RFs). OBJECTIVE: Circulating progenitor cell (PC) levels reflect endogenous regenerative potential. The effect on PC of healthy aging compared with aging with RFs or cardiovascular disease (CVD) is unknown. We examined whether exposure to RF and CVD leads to an accelerated decline in circulating PC with increasing age. METHODS AND RESULTS: In 2792 adult subjects, 498 were free of RFs (smoking, diabetes mellitus, hypertension, or hyperlipidemia), 1036 subjects had 1 to 2 RF, and 1253 had ≥3 RFs or CVD. PC were enumerated by flow cytometry as CD45(med+) mononuclear cells expressing CD34 and subsets coexpressing CD133, CXCR4, and vascular endothelial growth factor receptor-2 epitopes. Younger age, male sex, and larger body size correlated with higher PC counts (P<0.01). After multivariable adjustment, both age and RF categories were independently associated with PC counts (P<0.05), with lower PC counts in older subjects and those with higher RF burden or CVD. PC counts remained unchanged with increasing age in healthy individuals. There were significant interactions between age and RF categories (P≤0.005), such that for younger subjects (<40 years), RFs were associated with increased PC counts, whereas for older subjects (>60 years), RFs and CVD were associated with lower PC counts. CONCLUSIONS: Circulating PC levels do not decline with healthy aging; RF exposure at a younger age stimulates PC mobilization, whereas continued exposure is associated with lower PC levels in later life. Over the lifespan, exposure to RFs and CVD is associated with an initial stimulation and subsequent decline in circulating PC levels, which reflect endogenous regenerative capacity.
RATIONALE: We investigated aging of human endogenous reparative capacity and aimed to clarify whether it is affected by presence of cardiovascular disease or its risk factors (RFs). OBJECTIVE: Circulating progenitor cell (PC) levels reflect endogenous regenerative potential. The effect on PC of healthy aging compared with aging with RFs or cardiovascular disease (CVD) is unknown. We examined whether exposure to RF and CVD leads to an accelerated decline in circulating PC with increasing age. METHODS AND RESULTS: In 2792 adult subjects, 498 were free of RFs (smoking, diabetes mellitus, hypertension, or hyperlipidemia), 1036 subjects had 1 to 2 RF, and 1253 had ≥3 RFs or CVD. PC were enumerated by flow cytometry as CD45(med+) mononuclear cells expressing CD34 and subsets coexpressing CD133, CXCR4, and vascular endothelial growth factor receptor-2 epitopes. Younger age, male sex, and larger body size correlated with higher PC counts (P<0.01). After multivariable adjustment, both age and RF categories were independently associated with PC counts (P<0.05), with lower PC counts in older subjects and those with higher RF burden or CVD. PC counts remained unchanged with increasing age in healthy individuals. There were significant interactions between age and RF categories (P≤0.005), such that for younger subjects (<40 years), RFs were associated with increased PC counts, whereas for older subjects (>60 years), RFs and CVD were associated with lower PC counts. CONCLUSIONS: Circulating PC levels do not decline with healthy aging; RF exposure at a younger age stimulates PC mobilization, whereas continued exposure is associated with lower PC levels in later life. Over the lifespan, exposure to RFs and CVD is associated with an initial stimulation and subsequent decline in circulating PC levels, which reflect endogenous regenerative capacity.
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: 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: Gian Paolo Fadini; Shoichi Maruyama; Takenori Ozaki; Akihiko Taguchi; James Meigs; Stefanie Dimmeler; Andreas M Zeiher; Saula de Kreutzenberg; Angelo Avogaro; Georg Nickenig; Caroline Schmidt-Lucke; Nikos Werner Journal: PLoS One Date: 2010-07-09 Impact factor: 3.240
Authors: Florian H Seeger; Tina Rasper; Masamichi Koyanagi; Henrik Fox; Andreas M Zeiher; Stefanie Dimmeler Journal: Arterioscler Thromb Vasc Biol Date: 2009-08-20 Impact factor: 8.311
Authors: Ibhar Al Mheid; Frank Corrigan; Farheen Shirazi; Emir Veledar; Qunna Li; Wayne R Alexander; W Robert Taylor; Edmund K Waller; Arshed A Quyyumi Journal: J Am Heart Assoc Date: 2014-05-15 Impact factor: 5.501
Authors: Ayman Samman Tahhan; Muhammad Hammadah; Mohamad Raad; Zakaria Almuwaqqat; Ayman Alkhoder; Pratik B Sandesara; Heval Mohamed-Kelli; Salim S Hayek; Jeong Hwan Kim; Wesley T O'Neal; Matthew L Topel; Aubrey J Grant; Nabil Sabbak; Robert E Heinl; Mohamad Mazen Gafeer; Malik Obideen; Belal Kaseer; Nasser Abdelhadi; Yi-An Ko; Chang Liu; Iraj Hesaroieh; Ernestine A Mahar; Viola Vaccarino; Edmund K Waller; Arshed A Quyyumi Journal: Circ Res Date: 2018-03-07 Impact factor: 17.367
Authors: Muhammad Hammadah; Ibhar Al Mheid; Kobina Wilmot; Ronnie Ramadan; Naser Abdelhadi; Ayman Alkhoder; Malik Obideen; Pratik M Pimple; Oleksiy Levantsevych; Heval M Kelli; Amit Shah; Yan V Sun; Brad Pearce; Michael Kutner; Qi Long; Laura Ward; Yi-An Ko; Kareem Hosny Mohammed; Jue Lin; Jinying Zhao; J Douglas Bremner; Jinhee Kim; Edmund K Waller; Paolo Raggi; David Sheps; Arshed A Quyyumi; Viola Vaccarino Journal: Circ Res Date: 2016-12-12 Impact factor: 17.367