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

Department of Pharmaceutical Sciences

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

4 Scopus citations

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
State	Published - 1 Jul 2016

Bibliographical note

Publisher Copyright:
© 2016, Springer-Verlag Wien.

Keywords

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

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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",

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AU - Park, Subin

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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

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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.

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KW - Matrix metalloproteinase

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KW - Vascular endothelial growth factor receptor

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

Abstract

Bibliographical note

Keywords

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