P01HL152951
Project Grant
Overview
Grant Description
Perivascular Adipose Tissue (PVAT) as a Central Integrator of Vascular Health - Summary
Overall vascular health is essential to the normal regulation of cardiovascular function. That dysfunctions of blood pressure regulation, such as hypertension, remain difficult to treat suggests that the scientific community does not fully understand the mechanisms by which normal and pathological changes in blood pressure are achieved, nor how the vasculature can both influence and be impacted by changes in blood pressure.
This new program project grant is based on the overall hypothesis that perivascular adipose tissue (PVAT) has bidirectional interactions with the other layers of a blood vessel and is a critical partner with these layers to form an integrated system that maintains vascular health. Our collective preliminary work has led to the hypothesis that PVAT and its primary components - the adipocyte and progenitor cells, the immune cells, and neuronal innervation/neurohumoral control - are central integrators of overall vascular health/function.
This grant will enable foundational studies that are critical to understanding how the elements of PVAT work together and ultimately influence vascular tone. This grant is unique in that it will also interrogate how (patho)physiological challenges (e.g. change in stretch, pressure) placed on a vessel affect PVAT function. Our studies will progress to a model of high-fat (HF)-diet induced hypertension, a situation of elevated vascular pressure and PVAT burden.
This work will use models that allow for the most rigorous experimentation: mice in nerve- and adipocyte progenitor lineage-tracing; optogenetic and chemogenetic approaches; rats as a model organism for HF-diet induced hypertension; pressure imposition through a novel mid-thoracic aortic coarcted model; novel microscopic and bioinformatic work; and human vasculature + PVAT for translational potential.
Our collective, novel approach contrasts directly with the plethora of literature that investigates how the PVAT secretome influences vascular function. We will determine, through projects supported by four cores (administrative, animal, bioinformatic, and microscopy), whether: 1) PVAT possesses the ability to mechanotransduce and has significant stiffness that contributes to vascular stiffness; 2) PVAT is innervated or under neurohumoral control with functional consequence; 3) whether the unique microenvironment of PVAT influences immune cell function; and 4) how the fate of adipocyte progenitors is influenced by vascular stretch.
Investigators are deeply invested in the planning of, execution of, and learning from experiments carried out in projects and cores other than theirs; this work was purposely developed in this way to be synergistic. This integrated work advances human health by redefining the functional vessel, a redefinition that could have significant impact on not only hypertension but all physiologies and dysfunctions which involve the vasculature.
Overall vascular health is essential to the normal regulation of cardiovascular function. That dysfunctions of blood pressure regulation, such as hypertension, remain difficult to treat suggests that the scientific community does not fully understand the mechanisms by which normal and pathological changes in blood pressure are achieved, nor how the vasculature can both influence and be impacted by changes in blood pressure.
This new program project grant is based on the overall hypothesis that perivascular adipose tissue (PVAT) has bidirectional interactions with the other layers of a blood vessel and is a critical partner with these layers to form an integrated system that maintains vascular health. Our collective preliminary work has led to the hypothesis that PVAT and its primary components - the adipocyte and progenitor cells, the immune cells, and neuronal innervation/neurohumoral control - are central integrators of overall vascular health/function.
This grant will enable foundational studies that are critical to understanding how the elements of PVAT work together and ultimately influence vascular tone. This grant is unique in that it will also interrogate how (patho)physiological challenges (e.g. change in stretch, pressure) placed on a vessel affect PVAT function. Our studies will progress to a model of high-fat (HF)-diet induced hypertension, a situation of elevated vascular pressure and PVAT burden.
This work will use models that allow for the most rigorous experimentation: mice in nerve- and adipocyte progenitor lineage-tracing; optogenetic and chemogenetic approaches; rats as a model organism for HF-diet induced hypertension; pressure imposition through a novel mid-thoracic aortic coarcted model; novel microscopic and bioinformatic work; and human vasculature + PVAT for translational potential.
Our collective, novel approach contrasts directly with the plethora of literature that investigates how the PVAT secretome influences vascular function. We will determine, through projects supported by four cores (administrative, animal, bioinformatic, and microscopy), whether: 1) PVAT possesses the ability to mechanotransduce and has significant stiffness that contributes to vascular stiffness; 2) PVAT is innervated or under neurohumoral control with functional consequence; 3) whether the unique microenvironment of PVAT influences immune cell function; and 4) how the fate of adipocyte progenitors is influenced by vascular stretch.
Investigators are deeply invested in the planning of, execution of, and learning from experiments carried out in projects and cores other than theirs; this work was purposely developed in this way to be synergistic. This integrated work advances human health by redefining the functional vessel, a redefinition that could have significant impact on not only hypertension but all physiologies and dysfunctions which involve the vasculature.
Awardee
Funding Goals
TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Michigan
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 297% from $2,695,451 to $10,689,457.
Michigan State University was awarded
PVAT as Integrator of Vascular Health
Project Grant P01HL152951
worth $10,689,457
from National Heart Lung and Blood Institute in December 2021 with work to be completed primarily in Michigan United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Project Grant was awarded through grant opportunity NHLBI Program Project Applications (P01 Clinical Trials Optional).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
12/22/21
Start Date
11/30/26
End Date
Funding Split
$10.7M
Federal Obligation
$0.0
Non-Federal Obligation
$10.7M
Total Obligated
Activity Timeline
Transaction History
Modifications to P01HL152951
Additional Detail
Award ID FAIN
P01HL152951
SAI Number
P01HL152951-3656699902
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Funding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Awardee UEI
R28EKN92ZTZ9
Awardee CAGE
4B834
Performance District
MI-90
Senators
Debbie Stabenow
Gary Peters
Gary Peters
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $5,390,016 | 100% |
Modified: 8/20/25