Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells

Toyama, Yasuyuki; Sasaki, Ken-ichiro; Tachibana, Katsuro; Ueno, Takayoshi; Kajimoto, Hidemi; Yokoyama, Shinji; Ohtsuka, Masanori; Koiwaya, Hiroshi; Nakayoshi, Takaharu; Mitsutake, Yoshiaki; Chibana, Hidetoshi; Isobe, Naoki; Imaizumi, Tsutomu

doi:10.1093/cvr/cvs173

Cited by 24 publications

(26 citation statements)

References 41 publications

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“…Xu et al reported that LIPUS stimulated hematopoietic stem/progenitor cell viability, proliferation and differentiation in vitro [22]. Toyama et al also reported that application of LIPUS to circulating angiogenic cells augmented their generation and migration capacities [23]. Thus, it is possible that the LIPUS directly and/or indirectly affects the function and dynamics of immature cells, such as bone marrow-derived mononuclear cells and residential cardiac stem cells [24].…”

Section: Discussionmentioning

confidence: 99%

Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

et al. 2014

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BackgroundAlthough a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD.Methods and ResultsWe first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group.ConclusionsThese results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

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Section: Discussionmentioning

confidence: 99%

Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

et al. 2014

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“…Healthy angiogenesis is crucial for vascular regeneration (Toyama et al, 2012) and wound healing (Marrotte et al, 2010), whereas excessive angiogenesis contributes to inflammation (Hirono et al, 2009), atherosclerosis (Holm et al, 2009), and diabetic retinopathy (Titchenell and Antonetti, 2013). We use the term CACs rather than early EPCs, because although CACs exhibit endothelial qualities, CAC cultures consist predominantly of monocytic cells (Heiss et al, 2010), and their therapeutic effects are mediated by paracrine secretion of growth factors and antioxidants (Di Santo et al, 2009; Marrotte et al, 2010), rather than by endothelial differentiation (Hirschi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Among healthy individuals without cardiovascular disease or diabetes, reduced CAC migration prospectively predicts greater carotid artery intima-media thickness (Keymel et al, 2008) and correlates with metabolic risk factors (Aschbacher et al, 2012a) and better endothelial function (Van Craenenbroeck et al, 2010). In animals, delivering CACs or CAC-conditioned media to sites of ischemic vascular injury can regenerate damaged tissue (Kalka et al, 2000; Di Santo et al, 2009; Ma et al, 2009; Toyama et al, 2012; O’Loughlin et al, 2013). Hence, CAC function is more than a “biomarker,” it is a mechanism of vascular repair.…”

Section: Introductionmentioning

confidence: 99%

Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo

Aschbacher

Derakhshandeh

Flores

et al. 2016

Psychoneuroendocrinology

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Psychological stress and glucocorticoids are associated with heightened cardiovascular disease risk. We investigated whether stress or cortisol would be associated with reduced circulating angiogenic cell (CAC) function, an index of impaired vascular repair. We hypothesized that minority-race individuals who experience threat in interracial interactions would exhibit reduced CAC function, and that this link might be explained by cortisol. To test this experimentally, we recruited 106 African American participants for a laboratory interracial interaction task, in which they received socially evaluative feedback from Caucasian confederates. On a separate day, a subset of 32 participants (mean age = 26 years, 47% female) enrolled in a separate biological substudy and provided blood samples for CAC isolation and salivary samples to quantify the morning peak in cortisol (the cortisol awakening response, CAR). CAC function was quantified using cell culture assays of migration to vascular endothelial growth factor (VEGF) and secretion of VEGF into the culture medium. Heightened threat in response to an interracial interaction and trait anxiety in vivo were both associated with poorer CAC migratory function in vitro. Further, threat and poorer sustained attention during the interracial interaction were associated with a higher CAR, which in turn, was related to lower CAC sensitivity to glucocorticoids. In vitro, higher doses of cortisol impaired CAC migratory function and VEGF protein secretion. The glucocorticoid receptor antagonist RU486 reversed this functional impairment. These data identify a novel, neuroendocrine pathway by which psychological stress may reduce CAC function, with potential implications for cardiovascular health.

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“…Xu et al reported that LIPUS stimulated hematopoietic stem/progenitor cell viability, proliferation and differentiation in vitro [22]. Toyama et al also reported that application of LIPUS to circulating angiogenic cells augmented their generation and migration capacities [23]. Thus, it is possible that the LIPUS directly and/or indirectly affects the function and dynamics of immature cells, such as bone marrowderived mononuclear cells and residential cardiac stem cells [24].…”

Section: Potential Mechanisms For Lipus-induced Angiogenesismentioning

confidence: 99%

Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

Hanawa

Ito

Aizawa

et al. 2012

Journal of Cardiac Failure

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Ultrasound stimulation restores impaired neovascularization-related capacities of human circulating angiogenic cells

Abstract: Therapeutic angiogenesis with LIPUS-pre-treated CACs may be a new strategy to rescue critical limb ischaemia in atherosclerotic patients.

Cited by 24 publications

References 41 publications

Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo

Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

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