Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury

Edmund B. Chen; Katherine E. Shapiro; Kelly Wun; Thomas Kuntz; Betty R. Theriault; Michael J. Nooromid; Vanessa A. Leone; Katharine G. Harris; Qun Jiang; Melanie Spedale; Liqun Xiong; Jack A. Gilbert; Eugene B. Chang; Karen J. Ho

doi:10.1161/JAHA.119.013496

Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury

Edmund B. Chen, Katherine E. Shapiro, Kelly Wun, Thomas Kuntz, Betty R. Theriault, Michael J. Nooromid, Vanessa A. Leone, Katharine G. Harris, Qun Jiang, Melanie Spedale, Liqun Xiong, Jack A. Gilbert, Eugene B. Chang, Karen J. Ho^*

^*Corresponding author for this work

Surgery, Vascular Surgery Division

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

4 Scopus citations

Abstract

Background-—The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results-—We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions-—Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.

Original language	English (US)
Article number	e013496
Journal	Journal of the American Heart Association
Volume	9
Issue number	5
DOIs	https://doi.org/10.1161/JAHA.119.013496
State	Published - 2020

Funding

This work was supported by the National Heart, Lung, and Blood Institute (grant numbers K08HL130601 to Dr Ho, T32HL094293 to Drs Chen and Nooromid, R34HL136991 to Dr Gilbert), National Institute of Diabetes and Digestive and Kidney Diseases (grant numbers T32DK007074, R01DK097268, R56DK102872, and P30DK42086 to Dr Chang; K01DK111785 to Dr Leone, F32DK113743 to Dr Harris, R01DK111848, and U01DK106786 to Dr Gilbert), National Institute of Nursing Research (grant number R01NR015446 to Dr Gilbert), National Institute of Child Health and Human Development (grant number R03HD095056 to Dr Gilbert), National Institute of General Medical Sciences (grant number R01GM062344 to Dr Gilbert), the National Center for Advancing Translational Sciences (grant number UL1TR001422 to Drs Ho, Chen and Nooromid), Abbott Fund (Fellowship to Drs Chen and Nooromid), American College of Surgeons (Mentored Clinical Scientist Research Career Development Award to Dr Ho); and Society for Vascular Surgery (Mentored Clinical Scientist Research Career Development Award to Dr Ho). Advanced microscopy was performed in the Analytical bioNanoTechnol-ogy Core Facility of the Simpson Querrey Institute at North-western University. The US Army Research Office, the US Army Medical Research and Material Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental Resource (National Science Foundation Division of Electrical, Communications and Cyber Systems grant number 1542205).

Keywords

Microbiome
Neointimal hyperplasia
Restenosis

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/JAHA.119.013496

Cite this

Chen, E. B., Shapiro, K. E., Wun, K., Kuntz, T., Theriault, B. R., Nooromid, M. J., Leone, V. A., Harris, K. G., Jiang, Q., Spedale, M., Xiong, L., Gilbert, J. A., Chang, E. B., & Ho, K. J. (2020). Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury. Journal of the American Heart Association, 9(5), Article e013496. https://doi.org/10.1161/JAHA.119.013496

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title = "Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury",

abstract = "Background-—The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results-—We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions-—Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.",

keywords = "Microbiome, Neointimal hyperplasia, Restenosis",

author = "Chen, {Edmund B.} and Shapiro, {Katherine E.} and Kelly Wun and Thomas Kuntz and Theriault, {Betty R.} and Nooromid, {Michael J.} and Leone, {Vanessa A.} and Harris, {Katharine G.} and Qun Jiang and Melanie Spedale and Liqun Xiong and Gilbert, {Jack A.} and Chang, {Eugene B.} and Ho, {Karen J.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative.",

year = "2020",

doi = "10.1161/JAHA.119.013496",

language = "English (US)",

volume = "9",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

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Chen, EB, Shapiro, KE, Wun, K, Kuntz, T, Theriault, BR, Nooromid, MJ, Leone, VA, Harris, KG, Jiang, Q, Spedale, M, Xiong, L, Gilbert, JA, Chang, EB & Ho, KJ 2020, 'Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury', Journal of the American Heart Association, vol. 9, no. 5, e013496. https://doi.org/10.1161/JAHA.119.013496

TY - JOUR

T1 - Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury

AU - Chen, Edmund B.

AU - Shapiro, Katherine E.

AU - Wun, Kelly

AU - Kuntz, Thomas

AU - Theriault, Betty R.

AU - Nooromid, Michael J.

AU - Leone, Vanessa A.

AU - Harris, Katharine G.

AU - Jiang, Qun

AU - Spedale, Melanie

AU - Xiong, Liqun

AU - Gilbert, Jack A.

AU - Chang, Eugene B.

AU - Ho, Karen J.

PY - 2020

Y1 - 2020

N2 - Background-—The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results-—We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions-—Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.

AB - Background-—The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results-—We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions-—Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.

KW - Microbiome

KW - Neointimal hyperplasia

KW - Restenosis

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Microbial colonization of germ-free mice restores neointimal hyperplasia development after arterial injury

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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