In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes

Subin Park; Jangwook Lee; Mi hee Jo; Jin Hee Na; Sung Gurl Park; Hyeon Ki Jang; Sun Woong Kang; Jong Ho Kim; Byung Soo Kim; Jae Hyung Park; Ick Chan Kwon; Ju Hee Ryu; Kwangmeyung Kim

doi:10.1007/s00726-016-2225-0

In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes

Subin Park, Jangwook Lee, Mi hee Jo, Jin Hee Na, Sung Gurl Park, Hyeon Ki Jang, Sun Woong Kang, Jong Ho Kim, Byung Soo Kim, Jae Hyung Park, Ick Chan Kwon, Ju Hee Ryu, Kwangmeyung Kim

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.

Original language	English
Pages (from-to)	1641-1654
Number of pages	14
Journal	Amino Acids
Volume	48
Issue number	7
DOIs	https://doi.org/10.1007/s00726-016-2225-0
Publication status	Published - 2016 Jul 1

Bibliographical note

Funding Information:
This work was supported by Nano-Convergence Foundation ( www.nanotech2020.org ) funded by the Ministry of Science, ICT and Future Planning (MSIP, Korea) & the Ministry of Trade, Industry and Energy (MOTIE, KOREA) [project name: Development and Commercialization of Nanoparticle Sensor for Detecting Protease Activity], Development of High Medical Technology Project (HI14C2755) of KHIDI, and the Intramural Research Programs of KIST.

Publisher Copyright:
© 2016, Springer-Verlag Wien.

Keywords

Angiogenesis
Fluorescence imaging
Matrix metalloproteinase
Molecular imaging
Vascular endothelial growth factor receptor

ASJC Scopus subject areas

Biochemistry
Clinical Biochemistry
Organic Chemistry

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10.1007/s00726-016-2225-0

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title = "In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes",

abstract = "Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.",

keywords = "Angiogenesis, Fluorescence imaging, Matrix metalloproteinase, Molecular imaging, Vascular endothelial growth factor receptor",

author = "Subin Park and Jangwook Lee and Jo, {Mi hee} and Na, {Jin Hee} and Park, {Sung Gurl} and Jang, {Hyeon Ki} and Kang, {Sun Woong} and Kim, {Jong Ho} and Kim, {Byung Soo} and Park, {Jae Hyung} and Kwon, {Ick Chan} and Ryu, {Ju Hee} and Kwangmeyung Kim",

note = "Funding Information: This work was supported by Nano-Convergence Foundation ( www.nanotech2020.org ) funded by the Ministry of Science, ICT and Future Planning (MSIP, Korea) & the Ministry of Trade, Industry and Energy (MOTIE, KOREA) [project name: Development and Commercialization of Nanoparticle Sensor for Detecting Protease Activity], Development of High Medical Technology Project (HI14C2755) of KHIDI, and the Intramural Research Programs of KIST. Publisher Copyright: {\textcopyright} 2016, Springer-Verlag Wien.",

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AU - Park, Subin

AU - Lee, Jangwook

AU - Jo, Mi hee

AU - Na, Jin Hee

AU - Park, Sung Gurl

AU - Jang, Hyeon Ki

AU - Kang, Sun Woong

AU - Kim, Jong Ho

AU - Kim, Byung Soo

AU - Park, Jae Hyung

AU - Kwon, Ick Chan

AU - Ryu, Ju Hee

AU - Kim, Kwangmeyung

N1 - Funding Information: This work was supported by Nano-Convergence Foundation ( www.nanotech2020.org ) funded by the Ministry of Science, ICT and Future Planning (MSIP, Korea) & the Ministry of Trade, Industry and Energy (MOTIE, KOREA) [project name: Development and Commercialization of Nanoparticle Sensor for Detecting Protease Activity], Development of High Medical Technology Project (HI14C2755) of KHIDI, and the Intramural Research Programs of KIST. Publisher Copyright: © 2016, Springer-Verlag Wien.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.

AB - Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.

KW - Angiogenesis

KW - Fluorescence imaging

KW - Matrix metalloproteinase

KW - Molecular imaging

KW - Vascular endothelial growth factor receptor

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SN - 0939-4451

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JF - Amino Acids

IS - 7

ER -

In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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