# Ischemia/Reperfusion injury and Myocardial edema

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $645,489

## Abstract

Project Summary
Uncontrolled inflammation is a key driver of acute and chronic cardiovascular pathology.
However, the accompanying edema, one of the four cardinal signs of inflammation defined by
Celsus and Galen two millennia ago, is poorly understood and often ignored at the mechanistic
level. Yet ample evidence shows its causal roles in ischemia reperfusion injury (IRI) and
resultant sequelae in the heart, brain, and other organs.
While a number of molecules can induce edema formation, vascular endothelial growth factor
(VEGF), also known as vascular permeability factor (VPF) has been viewed as the key
component of IRI-associated edema development. There are a number of drugs capable of
blocking VEGF signaling, including vascular permeability that are widely used as anti-
angiogenic cancer and ophthalmologic drugs such as bevacizumab, sorafenib, sunitinib and
pazopanib among others. However, none of them can be used in acute/chronic ischemia
settings due to the induced loss of blood vasculature.
Exciting new data from our lab have demonstrated that it is possible to selectively block VEGF-
induced permeability defects without affecting other aspects of its signaling, thereby eliminating
anti-angiogenic effects of non-selective anti-VEGF therapies. In preliminary studies, blocking
VEGF-blocking edema formation leads to a ~50% reduction in the size of myocardial infarction
and preservation of LV systolic and diastolic function and suppression of VT inducibility. With
these preliminary results in hand, we propose to examine the functional effects myocardial
edema and evaluate the effect of anti-edema therapies in this setting.

## Key facts

- **NIH application ID:** 10869983
- **Project number:** 5R01HL169520-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael Simons
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,489
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869983

## Citation

> US National Institutes of Health, RePORTER application 10869983, Ischemia/Reperfusion injury and Myocardial edema (5R01HL169520-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869983. Licensed CC0.

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