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Multi-Scale Integration of Extracellular Matrix Mechanics in Vascular Remodeling

Award Number: R01HL098028
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2010
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Multi-Scale Integration of Extracellular Matrix Mechanics in Vascular Remodeling - PROJECT SUMMARY Aortic dissection (AD) is a devastating cardiovascular disease known for its rapid propagation and high morbidity and mortality. Diagnosis of the initial presentation of AD is a challenge because the symptoms are similar to those of many other health problems. In the absence of intervention, AD results in a mortality rate of up to 90%, with most of these deaths occurring within 48 hours of the onset of AD. AD is among the top 20 causes of death in the US, with 20-40% of patients die even before reaching hospital. There is a clear problem in our ability to manage AD patients in their crucial initial stage of development and to develop strategies for a timely treatment. AD usually initiates at a focal region that shows disrupted microarchitecture and compromised mechanical properties. Once dissected, the mechanical behavior of the separated aortic wall tissues become greatly affected, suggesting that layering discontinuity may play a role in triggering AD. Considering these distinct mechanical processes, we expect that understanding the evolvement of the focal and layering abnormalities may provide useful insights into the development of early diagnostic and intervention. The goal of this proposed research is to advance our understanding of the important role of local tissue mechanical properties and microstructures of the arterial wall in in the initiation and progression of AD. Large elastic arteries consist of concentric layers of elastic lamellae with inhomogeneously distributed elastic and collagen extracellular matrix (ECM) fibers. Our recent studies revealed several previously unrecognized findings, which provide strong evidence that ECM inhomogeneity is physiologically important. The overarching hypothesis of this proposed research is that the evolvement of inhomogeneity in local mechanical properties and ECM microstructure, both along and across the arterial wall, are triggering factors of AD. We will test this hypothesis using state-of-the-art quantitative ECM imaging, noninvasive local mechanical property mapping, discrete-finite element modelling, and tissue testing and validation with three aims: Specific Aim 1: To establish mappings of local ECM structure and mechanical properties of human thoracic aorta with sub-millimeter resolution. Specific Aim 2: To investigate the depth- and region-dependence of aortic layer delamination. Specific Aim 3: To create a computational model that incorporates ECM structural inhomogeneity and local wall mechanical properties to predict the propensity of AD. The knowledge we gain from this research is expected to provide insights into biomechanical markers useful for the diagnosis and treatment of AD. The new biomechanical markers considering local structural and mechanical inhomogeneities will identify the origin and propensity of AD with direct clinical impact on the developments of new early diagnostics and interventions.


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 = $530,031 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	001	12	8/15/2025	NON-COMPETING CONTINUATION	$530,031
2025	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	8	1/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $530,031

Issue Date FY: 2024 ( Subtotal = $519,431 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	11	8/9/2024	NON-COMPETING CONTINUATION	$519,431
														Subtotal = $519,431

Issue Date FY: 2023 ( Subtotal = $530,031 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	10	8/18/2023	NON-COMPETING CONTINUATION	$530,031
														Subtotal = $530,031

Issue Date FY: 2022 ( Subtotal = $552,881 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	9	6/7/2022	COMPETING CONTINUATION	$552,881
														Subtotal = $552,881

Issue Date FY: 2020 ( Subtotal = $414,300 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	8	8/19/2020	NON-COMPETING CONTINUATION	$414,300
														Subtotal = $414,300

Issue Date FY: 2019 ( Subtotal = $414,300 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	7	8/11/2019	NON-COMPETING CONTINUATION	$414,300
														Subtotal = $414,300

Issue Date FY: 2018 ( Subtotal = $662,986 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	6	8/17/2018	NON-COMPETING CONTINUATION	$414,300
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	001	6	9/17/2018	SUPPLEMENT FOR EXPANSION	$248,686
														Subtotal = $662,986

Issue Date FY: 2017 ( Subtotal = $429,529 )
2017	2017	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	5	8/11/2017	COMPETING CONTINUATION	$429,529
														Subtotal = $429,529

Issue Date FY: 2014 ( Subtotal = $280,746 )
2014	2014	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	001	4	5/8/2014	NON-COMPETING CONTINUATION	$22,918
2014	2014	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	4	11/28/2013	NON-COMPETING CONTINUATION	$257,828
														Subtotal = $280,746

Issue Date FY: 2013 ( Subtotal = $272,724 )
2013	2013	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	3	11/30/2012	NON-COMPETING CONTINUATION	$257,828
2013	2013	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	001	3	7/10/2013	NON-COMPETING CONTINUATION	$14,896
														Subtotal = $272,724

Issue Date FY: 2012 ( Subtotal = $286,271 )
2012	2012	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	001	2	2/29/2012	NON-COMPETING CONTINUATION	$28,627
2012	2012	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	12/14/2011	NON-COMPETING CONTINUATION	$257,644
														Subtotal = $286,271

Issue Date FY: 2011 ( Subtotal = $285,104 )
2011	2011	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	12/3/2010	NEW	$285,104
														Subtotal = $285,104

Grand Total All Awards = $5,178,334

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Multi-Scale Integration of Extracellular Matrix Mechanics in Vascular Remodeling

Award Number: R01HL098028

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2010

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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