title: Platelet-derived microparticles augment the adhesion and neovascularization capacities of circulating angiogenic cells obtained from atherosclerotic patients.
abstract: OBJECTIVE
  The neovascularization-related capacities of circulating angiogenic cells (CACs) are impaired in atherosclerotic patients, which may explain the unsatisfactory effects of therapeutic angiogenesis with atherosclerotic patient-derived CACs. Platelet-derived microparticles (PMPs) were reported to augment the re-endothelialization capacity of CACs. Accordingly, we investigated whether PMPs could augment the neovascularization-related capacities of atherosclerotic patient-derived CACs in vitro and in vivo and if so, the associated mechanisms.
  
  
  RESULTS
  We isolated mononuclear cells and PMPs from atherosclerotic patient-derived peripheral blood and generated PMP-pretreated CACs (PMP-CACs) by co-culture of the mononuclear cells and PMPs. Although the migration capacity of PMP-CACs was similar to that of CACs, the adhesion capacity of PMP-CACs was greater. PMPs released RANTES into the culture medium, and the receptors were similarly expressed on the surfaces of CACs and PMP-CACs. Intravenous injection of PMP-CACs to rats with hindlimb ischemia augmented neovascularization of the ischemic limbs more than the injection of CACs. The number of PMP-CACs incorporated into the capillaries of the ischemic limbs was greater than that of incorporated CACs. The augmented adhesion and neovascularization capacities by PMP-CACs were canceled out by a RANTES neutralizing antibody.
  
  
  CONCLUSIONS
  PMP-secreted RANTES may play a role in the augmenting adhesion and neovascularization capacities of CACs. Injection of PMP-CACs may be a new strategy to augment the effects of therapeutic angiogenesis for limb ischemia in atherosclerotic patients.
authors: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Japan.
authors: Masanori
authors: M
authors: Ohtsuka
authors: Ken-ichiro
authors: K
authors: Sasaki
authors: Takafumi
authors: T
authors: Ueno
authors: Ritsuko
authors: R
authors: Seki
authors: Takaharu
authors: T
authors: Nakayoshi
authors: Hiroshi
authors: H
authors: Koiwaya
authors: Yasuyuki
authors: Y
authors: Toyama
authors: Shinji
authors: S
authors: Yokoyama
authors: Yoshiaki
authors: Y
authors: Mitsutake
authors: Hidetoshi
authors: H
authors: Chibana
authors: Naoki
authors: N
authors: Itaya
authors: Takashi
authors: T
authors: Okamura
authors: Tsutomu
authors: T
authors: Imaizumi
mesh_terms: D000328:Adult; D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology*; D002448:Cell Adhesion; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism; D005121:Extremities / Q000473:pathology; D005260:Female; D006801:Humans; D007511:Ischemia / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors
chemical_list: D018946:Chemokine CCL5