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Development of phospholipid-based nanotherapeutics for treating abdominal aortic aneurysm

Award Number: R01HL165688
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Development of phospholipid-based nanotherapeutics for treating abdominal aortic aneurysm - PROJECT SUMMARY/ABSTRACT Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular condition associated with high mortality rates upwards of 80% upon rupture. Vascular inflammation plays a primary role in AAA, with chronic inflammation and degradation of the extracellular matrix leading to segmental dilation of the aortic wall. However, clinical trials involving anti-inflammatory therapeutics have failed to yield meaningful results. Currently, there are no FDA- approved therapeutics to treat AAA. Our lab has demonstrated that treatment with synthetic high-density lipoprotein (sHDL) nanoparticles has a protective effect in AAA, leading to a nearly two-fold reduction in AAA incident and aortic diameter, highlighting the potential of sHDL for AAA treatment. Thus, the objective of this proposal is to determine the mechanism by which sHDL attenuates AAA pathogenesis and optimize formulation for effective treatment and delivery. We will accomplish this by 1) developing sHDL particles and determine underlying protective mechanisms against AAA in vitro. Specifically, the effects of sHDL will be assessed in vascular smooth muscle cells (VSMC), macrophages, endothelial cells. We will also 2) evaluate and optimize sHDL treatment in AAA mouse models. The successful completion of this present study will provide robust mechanistic insight into how sHDL attenuates AAA pathogenesis through its actions at VSMCs, endothelial cells and macrophages.


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: 2025 ( Subtotal = $0 )
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cardiovascular Diseases Research	000	2	6/5/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $829,992 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cardiovascular Diseases Research	001	2	9/13/2024	SUPPLEMENT FOR EXPANSION	$81,335
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cardiovascular Diseases Research	000	2	5/16/2024	NON-COMPETING CONTINUATION	$748,657
														Subtotal = $829,992

Issue Date FY: 2023 ( Subtotal = $763,935 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Cardiovascular Diseases Research	000	1	6/13/2023	NEW	$763,935
														Subtotal = $763,935

Grand Total All Awards = $1,593,927

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Development of phospholipid-based nanotherapeutics for treating abdominal aortic aneurysm

Award Number: R01HL165688

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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