title: Long-term individual shear rate therapy counterpulsation enhances plasma nitrite release in patients with PAD.
abstract: Individual shear rate therapy (ISRT) has been designed as a novel non-invasive treatment option for peripheral artery disease (PAD) patients and has been shown to improve endothelial function and walking distance. The aim of this study was to elucidate the impact of ISRT on the level of nitric oxide in patient blood plasma and the expression of related molecular markers in peripheral blood mononuclear cells (PBMCs). Molecular diagnostic tests were performed for two ISRT trials.
  
  
  
  In ISRT-1 26 healthy subjects underwent one session of treadmill training and one session of ISRT respectively in a cross-over design. In ISRT-2 14 PAD patients with a stable intermittent claudication underwent a 30 hours long-term treatment. Plasma nitrite release as well as the mRNA expression of NOS2 and key regulators of the kallikrein-kinin system were measured in PBMCs at different time points.
  
  
  
  Short-term ISRT revealed significantly decreased NOS2 expression in PBMCs of healthy volunteers and PAD patients. Long-term ISRT, in turn, demonstrated a significant plasma nitrite increase in PAD patients.
  
  
  
  We verified that long-term ISRT stimulates the vascular system and exerts a comparable effect to physical exercise in regards to NO release, which coincide with recent findings regarding an improvement of endothelial function. However, further studies are necessary to investigate the role for circulating leukocytes. .
authors.affiliation: a These authors contributed equally.|2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.
authors.forename: Michèle
authors.initials: M
authors.lastname: Brix
authors.affiliation: a These authors contributed equally.|1 Medical University of Brandenburg (MHB), Center for Internal Medicine I, Dept. for Angiology, Brandenburg an der Havel, Germany.|2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.|3 Charité-Universitaetsmedizin Berlin (CCM), Institute of Physiology, Berlin, Germany.
authors.forename: Eva-Elina
authors.initials: EE
authors.lastname: Buschmann
authors.affiliation: 2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zietzer
authors.affiliation: 2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.
authors.forename: Jonnel Anthony
authors.initials: JA
authors.lastname: Jaurigue
authors.affiliation: 1 Medical University of Brandenburg (MHB), Center for Internal Medicine I, Dept. for Angiology, Brandenburg an der Havel, Germany.|2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.affiliation: 2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Jungk
authors.affiliation: 1 Medical University of Brandenburg (MHB), Center for Internal Medicine I, Dept. for Angiology, Brandenburg an der Havel, Germany.|2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.|3 Charité-Universitaetsmedizin Berlin (CCM), Institute of Physiology, Berlin, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Buschmann
authors.affiliation: a These authors contributed equally.|4 Charité-Universitaetsmedizin Berlin (CVK), Berlin-Brandenburg School for Regenerative Therapies Berlin, Berlin, Germany.|5 FU Berlin, Institute for Chemistry and Biochemistry, Berlin, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Janke
authors.affiliation: a These authors contributed equally.|1 Medical University of Brandenburg (MHB), Center for Internal Medicine I, Dept. for Angiology, Brandenburg an der Havel, Germany.|2 Charité-Universitaetsmedizin Berlin (CCM), Center for Cardiovascular Research, Richard-Thoma-Laboratories for Arteriogenesis Berlin, Berlin, Germany.|3 Charité-Universitaetsmedizin Berlin (CCM), Institute of Physiology, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hillmeister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015908:Counterpulsation / Q000379:methods*; D018592:Cross-Over Studies; D005080:Exercise Test; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D016234:Kallikrein-Kinin System / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood / Q000235:genetics; D009573:Nitrites / Q000097:blood*; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D013314:Stress, Mechanical; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009573:Nitrites; D012333:RNA, Messenger; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Peripheral vascular disease; exercise; exercise testing; gene expression endothelium; nitric oxide; rehabilitation; vascular type