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Angiogenesis in Wound Repair

Award Number: R01GM050875
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/1994
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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Angiogenesis in Wound Repair - In skin wounds, angiogenesis is characterized by the abundant growth of new capillaries, ultimately creating a vascular bed that is several times denser than normal tissue. As the wound resolves, most of these excess vessels are removed, and the vascular content returns to a near normal state. While it has long been assumed that a high level of capillary growth is essential for optimal healing, recent studies by us and others challenge that notion. Our data suggests that normally healing wounds exhibit an overly robust and largely dysfunctional angiogenic response that has detrimental effects on repair outcomes. Our work demonstrates that pharmacologic treatments that establish a more refined and immediately functional vasculature improve healing and reduce scar formation. A possible mechanism by which the normally vigorous angiogenic response might spur scarring and fibrosis in wounds is via apoptotic endothelial cells. During wound resolution, a substantial apoptotic endothelial cell load is created when capillaries are pruned back to normal levels. Our preliminary data shows that apoptotic endothelial cells (EC) can directly influence fibroblast function, thereby connecting vascular overgrowth, vascular regression, EC apoptotic load, and scar formation. The central concept that underpins this application is that pharmacologic treatments that force the rapid development of a mature vasculature support ideal healing, in part by reducing the apoptotic EC load. Aim 1 will advance toward clinical trials by a) assessing the effect of a pharmacologic reduction of angiogenesis in a clinically relevant rabbit model of hypertrophic scar formation, and b) surveying vascular content and maturity in human scar tissues. Aims 2 and 3 address the central hypothesis that apoptotic EC directly influence wound resolution and outcomes. Aim 2 will identify factors produced by apoptotic EC that provoke wound fibrosis. Aim 3 will examine how apoptotic EC are cleared from wounds, and will establish how engulfment of apoptotic EC bodies affects wound resolution. The proposed work is innovative because it addresses the unique clinical approach of down-regulating the angiogenic response in wounds to reduce scar formation. Further innovation comes from the examination of the influence of apoptotic EC, as the effect of the considerable endothelial apoptotic load that occurs during wound resolution is almost entirely unstudied. The significance of this research lies in the potential application to the clinical problems of hypertrophic scars and other fibrotic diseases. The findings will support our long term goal of understanding the regulation of wound angiogenesis in health and disease, and of capitalizing upon this knowledge to improve wound healing outcomes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	27	4/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	27	7/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $403,434 )
2020	2020	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	27	7/16/2020	NON-COMPETING CONTINUATION	$403,434
														Subtotal = $403,434

Issue Date FY: 2019 ( Subtotal = $399,750 )
2019	2019	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	001	26	9/18/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	26	7/31/2019	NON-COMPETING CONTINUATION	$399,750
														Subtotal = $399,750

Issue Date FY: 2018 ( Subtotal = $432,010 )
2018	2018	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	001	25	7/18/2018	NON-COMPETING CONTINUATION	$432,010
2018	2015	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	23	6/19/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $432,010

Issue Date FY: 2017 ( Subtotal = $399,750 )
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	24	8/7/2017	COMPETING CONTINUATION	$399,750
														Subtotal = $399,750

Issue Date FY: 2015 ( Subtotal = $336,545 )
2015	2015	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	23	9/10/2015	NON-COMPETING CONTINUATION	$336,545
														Subtotal = $336,545

Issue Date FY: 2014 ( Subtotal = $336,545 )
2014	2014	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	22	8/25/2014	NON-COMPETING CONTINUATION	$336,545
														Subtotal = $336,545

Issue Date FY: 2013 ( Subtotal = $324,766 )
2013	2013	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	21	8/21/2013	NON-COMPETING CONTINUATION	$324,766
														Subtotal = $324,766

Issue Date FY: 2012 ( Subtotal = $336,545 )
2012	2012	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	20	9/10/2012	COMPETING CONTINUATION	$336,545
														Subtotal = $336,545

Issue Date FY: 2010 ( Subtotal = $325,674 )
2010	2010	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	19	7/30/2010	NON-COMPETING CONTINUATION	$325,674
														Subtotal = $325,674

Issue Date FY: 2009 ( Subtotal = $338,912 )
2009	2009	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	001	18	7/28/2009	NON-COMPETING CONTINUATION	$333,938
2009	2009	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	17	6/29/2009	SUPPLEMENT FOR EXPANSION	$4,974
														Subtotal = $338,912

Issue Date FY: 2008 ( Subtotal = $339,384 )
2008	2008	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	17	9/16/2008	NON-COMPETING CONTINUATION	$328,964
2008	2008	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	001	16	9/12/2008	SUPPLEMENT FOR EXPANSION	$10,420
														Subtotal = $339,384

Issue Date FY: 2007 ( Subtotal = $328,964 )
2007	2007	UNIVERSITY OF ILLINOIS AT CHICAGO	809 S MARSHFIELD AVE, 511 MB	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	16	9/17/2007	COMPETING CONTINUATION	$328,964
														Subtotal = $328,964

Issue Date FY: 2006 ( Subtotal = $302,715 )
2006	2006	UNIVERSITY OF ILLINOIS AT CHICAGO	809 S MARSHFIELD AVE, 511 MB	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	15	8/30/2006	NON-COMPETING CONTINUATION	$302,715
														Subtotal = $302,715

Issue Date FY: 2005 ( Subtotal = $296,000 )
2005	2005	LOYOLA UNIVERSITY MEDICAL CENTER							Biomedical Research and Research Training	000	13	8/26/2005	NON-COMPETING CONTINUATION	$296,000
														Subtotal = $296,000

Issue Date FY: 2004 ( Subtotal = $296,000 )
2004	2004	LOYOLA UNIVERSITY MEDICAL CENTER							Biomedical Research and Research Training	000	12	8/19/2004	NON-COMPETING CONTINUATION	$296,000
														Subtotal = $296,000

Issue Date FY: 2003 ( Subtotal = $532,707 )
2003	2003	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	10		NON-COMPETING CONTINUATION	$236,707
2003	2003	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	11	7/18/2003	COMPETING CONTINUATION	$296,000
														Subtotal = $532,707

Issue Date FY: 2002 ( Subtotal = $275,866 )
2002	2002	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	9	11/21/2001	NON-COMPETING CONTINUATION	$275,866
														Subtotal = $275,866

Issue Date FY: 2001 ( Subtotal = $319,370 )
2001	2001	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	8	1/15/2001	NON-COMPETING CONTINUATION	$267,921
2001	2001	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	001	8	4/2/2001	SUPPLEMENT FOR EXPANSION	$51,449
														Subtotal = $319,370

Issue Date FY: 2000 ( Subtotal = $260,208 )
2000	2000	LOYOLA UNIVERSITY OF CHICAGO	820 N MICHIGAN AVENUE	CHICAGO	IL	60611	COOK	USA	Biomedical Research and Research Training	000	7	1/31/2000	NON-COMPETING CONTINUATION	$260,208
														Subtotal = $260,208

Issue Date FY: 1999 ( Subtotal = $42,120 )
1999	1999	LOYOLA UNIVERSITY OF CHICAGO	820 N MICHIGAN AVENUE	CHICAGO	IL	60611	COOK	USA	Biomedical Research and Research Training	000	6	9/20/1999	COMPETING CONTINUATION	$42,120
														Subtotal = $42,120

Grand Total All Awards = $6,627,265

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Angiogenesis in Wound Repair

Award Number: R01GM050875

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/1994

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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