R01HL164983
Project Grant
Overview
Grant Description
Assessment of Mast Cell Degranulation in Infarcted Myocardium Using Quantitative Multiparametric MRI - Project Summary
The overall objective of the proposed project is to evaluate the effectiveness of a novel pharmacological treatment of myocardial infarction (MI) using quantitative multiparametric magnetic resonance imaging (QMRI). MI is a major cause of death and disability worldwide.
Urgent reperfusion of the occluded artery to restore myocardial blood flow is central to the clinical management of acute thrombotic MI (AMI). However, recanalization of the culprit artery may also result in unintended injury by causing microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and edema during the acute phase.
In the setting of chronic MI, iron deposition and fat accumulation (lipomatous metaplasia, LM) are frequently observed in infarcted myocardium. All these biomarkers are strong predictors of major adverse cardiovascular events such as heart failure. To date, however, there have been no effective therapeutic strategies for attenuating either MVO, IMH, chronic iron deposition, or LM post-reperfusion.
Mast cells (MC) are derived from blood-borne, multipotent hematopoietic progenitor cells that, once located in tissue, differentiate to a final phenotype under the influence of the local microenvironment. In general, MC exert their physiological and pathological functions by releasing cytoplasmic granules (degranulation) containing a variety of biologically active mediators.
Recent experimental studies have shown that hematoma growth, edema expansion, and overall neurological damage after cerebral ischemia-reperfusion can be reduced by early treatment with MC stabilizers, which are known to suppress MC degranulation. Equally important, atherosclerosis research over the last two decades has provided strong evidence for MC involvement in foam cell formation and plaque development.
Based on these studies, we hypothesized that MC stabilization via the administration of over-the-counter anti-allergy medication loratadine reduces myocardial edema, IMH volume, and improves myocardial microcirculation in the acute MI setting; and attenuates LM of infarcted myocardium in the chronic phase.
Quantitative cardiovascular MR (QCMR) imaging has been widely used to characterize myocardial ischemia, hemorrhage, edema, inflammation, iron deposition, fat accumulation, and other pathological conditions. In this proposal, we aim to validate the effectiveness of MC stabilizer loratadine on structural and functional cardiac remodeling post-pharmacotherapy in a porcine model of MI by temporally following imaging biomarkers of acute and chronic MI using well-established QCMR techniques.
Successful completion of the project will provide initial validation that early loratadine intervention has the potential to be a novel therapeutic strategy for prevention of heart failure post-MI as evaluated by our quantitative multiparametric MRI approach.
The overall objective of the proposed project is to evaluate the effectiveness of a novel pharmacological treatment of myocardial infarction (MI) using quantitative multiparametric magnetic resonance imaging (QMRI). MI is a major cause of death and disability worldwide.
Urgent reperfusion of the occluded artery to restore myocardial blood flow is central to the clinical management of acute thrombotic MI (AMI). However, recanalization of the culprit artery may also result in unintended injury by causing microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and edema during the acute phase.
In the setting of chronic MI, iron deposition and fat accumulation (lipomatous metaplasia, LM) are frequently observed in infarcted myocardium. All these biomarkers are strong predictors of major adverse cardiovascular events such as heart failure. To date, however, there have been no effective therapeutic strategies for attenuating either MVO, IMH, chronic iron deposition, or LM post-reperfusion.
Mast cells (MC) are derived from blood-borne, multipotent hematopoietic progenitor cells that, once located in tissue, differentiate to a final phenotype under the influence of the local microenvironment. In general, MC exert their physiological and pathological functions by releasing cytoplasmic granules (degranulation) containing a variety of biologically active mediators.
Recent experimental studies have shown that hematoma growth, edema expansion, and overall neurological damage after cerebral ischemia-reperfusion can be reduced by early treatment with MC stabilizers, which are known to suppress MC degranulation. Equally important, atherosclerosis research over the last two decades has provided strong evidence for MC involvement in foam cell formation and plaque development.
Based on these studies, we hypothesized that MC stabilization via the administration of over-the-counter anti-allergy medication loratadine reduces myocardial edema, IMH volume, and improves myocardial microcirculation in the acute MI setting; and attenuates LM of infarcted myocardium in the chronic phase.
Quantitative cardiovascular MR (QCMR) imaging has been widely used to characterize myocardial ischemia, hemorrhage, edema, inflammation, iron deposition, fat accumulation, and other pathological conditions. In this proposal, we aim to validate the effectiveness of MC stabilizer loratadine on structural and functional cardiac remodeling post-pharmacotherapy in a porcine model of MI by temporally following imaging biomarkers of acute and chronic MI using well-established QCMR techniques.
Successful completion of the project will provide initial validation that early loratadine intervention has the potential to be a novel therapeutic strategy for prevention of heart failure post-MI as evaluated by our quantitative multiparametric MRI approach.
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
Los Angeles,
California
900481804
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 295% from $834,798 to $3,298,936.
Cedars-Sinai Medical Center was awarded
MC Stabilization with Loratadine Post-MI Cardiac Remodeling - QMRI Study
Project Grant R01HL164983
worth $3,298,936
from National Heart Lung and Blood Institute in July 2022 with work to be completed primarily in Los Angeles California United States.
The grant
has a duration of 4 years and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
7/1/22
Start Date
6/30/26
End Date
Funding Split
$3.3M
Federal Obligation
$0.0
Non-Federal Obligation
$3.3M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01HL164983
Additional Detail
Award ID FAIN
R01HL164983
SAI Number
R01HL164983-4007030323
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An 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
NCSMA19DF7E6
Awardee CAGE
2F323
Performance District
CA-30
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
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) | $1,661,690 | 100% |
Modified: 8/20/25