Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia

被引:14
|
作者
Dopheide, Joern F. [1 ]
Geissler, Philipp [1 ]
Rubrech, Jennifer [1 ]
Trumpp, Amelie [1 ]
Zeller, Geraldine C. [2 ]
Bock, Karsten [1 ]
Dorweiler, Bernhard [5 ]
Duenschede, Friedrich [5 ]
Muenzel, Thomas [1 ]
Radsak, Markus P. [3 ,4 ]
Espinola-Klein, Christine [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med 2, D-55131 Mainz, Germany
[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med 1, D-55131 Mainz, Germany
[3] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med 3, D-55131 Mainz, Germany
[4] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, D-55131 Mainz, Germany
[5] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Cardiothorac & Vasc Surg, Div Vasc Surg, D-55131 Mainz, Germany
关键词
EPC; TEM; Peripheral arterial disease; Critical limb ischemia; Inflammation; PERIPHERAL ARTERIAL-DISEASE; CARDIOVASCULAR RISK-FACTORS; C-REACTIVE PROTEIN; TASK-FORCE; THERAPEUTIC ANGIOGENESIS; LOWER-EXTREMITY; GROWTH-FACTOR; GENE-THERAPY; POPULATION; EXPRESSION;
D O I
10.1007/s10456-015-9489-y
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells. Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months. In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = -0.266; p < 0.01) (EPC: r = -0.297; p < 0.001)], CRP (TEM: r = -0.283; p < 0.01) (EPC: r = -0.260; p < 0.01). We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.
引用
收藏
页码:67 / 78
页数:12
相关论文
共 40 条
  • [1] Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia
    Jörn F. Dopheide
    Philipp Geissler
    Jennifer Rubrech
    Amelie Trumpp
    Geraldine C. Zeller
    Karsten Bock
    Bernhard Dorweiler
    Friedrich Dünschede
    Thomas Münzel
    Markus P. Radsak
    Christine Espinola-Klein
    [J]. Angiogenesis, 2016, 19 : 67 - 78
  • [2] Pro-angiogenic efficacy of transplanting endothelial progenitor cells for treating hindlimb ischemia in hyperglycemic rabbits
    Yu, Ping
    Li, Qiang
    Liu, Ying
    Zhang, Jinchao
    Seldeen, Ken
    Pang, Manhui
    [J]. JOURNAL OF DIABETES AND ITS COMPLICATIONS, 2015, 29 (01) : 13 - 19
  • [3] Pro-angiogenic Terbium Hydroxide Nanorods Improve Critical Limb Ischemia in Part by Amelioration of Ischemia-Induced Endothelial Injury
    Basuthakur, Papia
    Roy, Arpita
    Ghosh, Soumya
    Vijay, Vincy
    Sinha, Debiprasad
    Radhakrishnan, Mydhili
    Kumar, Arvind
    Patra, Chitta Ranjan
    Chakravarty, Sumana
    [J]. ACS APPLIED BIO MATERIALS, 2024,
  • [4] The angiogenic potential of Tie2-expressing monocytes is impaired in patients with critical limb ischaemia
    Patel, A. S.
    Smith, A.
    Saha, P.
    Mattock, K.
    Humphries, J.
    Siow, R.
    Waltham, M.
    Modarai, B.
    [J]. BRITISH JOURNAL OF SURGERY, 2011, 98 : 2 - 2
  • [5] Pro-angiogenic Tie2-expressing monocytes/TEMs as a biomarker of the response to sorafenib in patients with advanced hepatocellular carcinoma
    Shoji, Hirotaka
    Yoshio, Sachiyo
    Mano, Yohei
    Sugiyama, Masaya
    Aoki, Yoshihiko
    Itokawa, Norio
    Atsukawa, Masanori
    Osawa, Yosuke
    Kimura, Kiminori
    Taketomi, Akinobu
    Mizokami, Masashi
    Kanto, Tatsuya
    [J]. HEPATOLOGY, 2015, 62 : 449A - 449A
  • [6] Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma
    Shoji, Hirotaka
    Yoshio, Sachiyo
    Mano, Yohei
    Doi, Hiroyoshi
    Sugiyama, Masaya
    Osawa, Yosuke
    Kimura, Kiminori
    Arai, Taeang
    Itokawa, Norio
    Atsukawa, Masanori
    Aoki, Yoshihiko
    Fukai, Moto
    Taketomi, Akinobu
    Mizokami, Masashi
    Kanto, Tatsuya
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2017, 141 (05) : 1011 - 1017
  • [7] Influence of exercise training on proangiogenic TIE-2 monocytes and circulating angiogenic cells in patients with peripheral arterial disease
    Jörn F. Dopheide
    Philipp Geissler
    Jennifer Rubrech
    Amelie Trumpp
    Geraldine C. Zeller
    Andreas Daiber
    Thomas Münzel
    Markus P. Radsak
    Christine Espinola-Klein
    [J]. Clinical Research in Cardiology, 2016, 105 : 666 - 676
  • [8] Influence of exercise training on proangiogenic TIE-2 monocytes and circulating angiogenic cells in patients with peripheral arterial disease
    Dopheide, Jorn F.
    Geissler, Philipp
    Rubrech, Jennifer
    Trumpp, Amelie
    Zeller, Geraldine C.
    Daiber, Andreas
    Muenzel, Thomas
    Radsak, Markus P.
    Espinola-Klein, Christine
    [J]. CLINICAL RESEARCH IN CARDIOLOGY, 2016, 105 (08) : 666 - 676
  • [9] Comprehensive analyses of serum biomarkers associating with the increase of pro-angiogenic Tie2-expressing monocytes in patients with hepatocellular carcinoma
    Shoji, Hirotaka
    Kanto, Tatsuya
    Mano, Yohei
    Aoki, Yoshihiko
    Yoshio, Sachiyo
    Sugiyama, Masaya
    Taketomi, Akinobu
    Mizokami, Masashi
    [J]. CANCER RESEARCH, 2015, 75
  • [10] The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production
    Monika Litwin
    Agata Radwańska
    Maria Paprocka
    Claudine Kieda
    Tadeusz Dobosz
    Wojciech Witkiewicz
    Dagmara Baczyńska
    [J]. Molecular and Cellular Biochemistry, 2015, 410 : 131 - 142