OBJECTIVE: Circulating angiogenic cells (CACs), also termed endothelial progenitor cells, play an integral role in vascular repair and are functionally impaired in coronary artery disease (CAD). The role of nitric oxide (NO) in CAC function is poorly understood. We hypothesized that CAC migration toward angiogenic signals is modulated by both NO synthase (NOS) expression and functional response to NO. METHODS AND RESULTS: Similar to endothelial cells, CAC chemotaxis to vascular endothelial growth factor (VEGF) was blocked by inhibition of NOS, phosphatidylinositol 3-kinase, or guanylyl cyclase or by treatment with an NO scavenger. Addition of an NO donor (S-nitroso-N-acetylpenicillamine) and the NOS substrate l-arginine increased random cell migration (chemokinesis) and enhanced VEGF-dependent chemotaxis. Healthy CACs expressed endothelial NOS, but endothelial NOS was not detected in CAD patient CACs. Both chemokinesis and chemotaxis to VEGF of patient CACs were decreased compared with healthy CACs but were restored to healthy values by S-nitroso-N-acetylpenicillamine. In parallel, CAD patients exhibited lower flow-mediated vasodilation and plasma NO source nitrite than young, healthy subjects, indicating endothelial dysfunction with reduced NO bioavailability. CONCLUSIONS: NOS activity is required for CAC chemotaxis. In CAD patients, impairment of NOS expression and NO bioavailability, rather than response to NO, may contribute to dysfunction of CACs and limit their regenerative capacity.
OBJECTIVE: Circulating angiogenic cells (CACs), also termed endothelial progenitor cells, play an integral role in vascular repair and are functionally impaired in coronary artery disease (CAD). The role of nitric oxide (NO) in CAC function is poorly understood. We hypothesized that CAC migration toward angiogenic signals is modulated by both NO synthase (NOS) expression and functional response to NO. METHODS AND RESULTS: Similar to endothelial cells, CAC chemotaxis to vascular endothelial growth factor (VEGF) was blocked by inhibition of NOS, phosphatidylinositol 3-kinase, or guanylyl cyclase or by treatment with an NO scavenger. Addition of an NO donor (S-nitroso-N-acetylpenicillamine) and the NOS substrate l-arginine increased random cell migration (chemokinesis) and enhanced VEGF-dependent chemotaxis. Healthy CACs expressed endothelial NOS, but endothelial NOS was not detected in CAD patient CACs. Both chemokinesis and chemotaxis to VEGF of patient CACs were decreased compared with healthy CACs but were restored to healthy values by S-nitroso-N-acetylpenicillamine. In parallel, CAD patients exhibited lower flow-mediated vasodilation and plasma NO source nitrite than young, healthy subjects, indicating endothelial dysfunction with reduced NO bioavailability. CONCLUSIONS: NOS activity is required for CAC chemotaxis. In CAD patients, impairment of NOS expression and NO bioavailability, rather than response to NO, may contribute to dysfunction of CACs and limit their regenerative capacity.
Authors: Thomas Thum; Dimitrios Tsikas; Sylvia Stein; Maximilian Schultheiss; Martin Eigenthaler; Stefan D Anker; Philip A Poole-Wilson; Georg Ertl; Johann Bauersachs Journal: J Am Coll Cardiol Date: 2005-10-10 Impact factor: 24.094
Authors: T Murohara; T Asahara; M Silver; C Bauters; H Masuda; C Kalka; M Kearney; D Chen; J F Symes; M C Fishman; P L Huang; J M Isner Journal: J Clin Invest Date: 1998-06-01 Impact factor: 14.808
Authors: Nathan T Jenkins; Rian Q Landers; Steven J Prior; Naina Soni; Espen E Spangenburg; James M Hagberg Journal: J Appl Physiol (1985) Date: 2011-06-23
Authors: Qiumei Chen; Richard E Sievers; Monika Varga; Sourabh Kharait; Daniel J Haddad; Aaron K Patton; Christopher S Delany; Sarah C Mutka; Joan P Blonder; Gregory P Dubé; Gary J Rosenthal; Matthew L Springer Journal: J Appl Physiol (1985) Date: 2013-01-24
Authors: Luc Bruyndonckx; Vicky Y Hoymans; Amaryllis H Van Craenenbroeck; Dirk K Vissers; Christiaan J Vrints; José Ramet; Viviane M Conraads Journal: Oxid Med Cell Longev Date: 2013-04-03 Impact factor: 6.543