# Therapeutic targeting of angiophagy to achieve microvascular recanalization

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $474,092

## Abstract

SUMMARY
Thromboembolic occlusions of the microvasculature are implicated in many acute ischemic conditions
including stroke and myocardial infarction and may be partly responsible for the “no-reflow“ phenomenon. The
fibrinolytic system and hemodynamic washout are considered the principal mechanisms for removing occlusive
thromboemboli in all vascular beds, however we have shown that they have a high failure rate at the
microvascular level. This may be partly due to a mechanism that we discovered and termed “angiophagy”,
whereby endothelial lamellipodia extensively envelop occluding emboli, trapping them within the vascular
lumen, markedly reducing hemodynamic washout and limiting access to plasma fibrinolytic enzymes. In
conditions such as stroke, it is likely that the early stage of thromboembolus engulfment is highly detrimental as
it prevents distal microvascular recanalization following spontaneous reopening of large occluded vessels or
after tissue plasminogen activator administration or mechanical thrombectomy. We hypothesize that
pharmacologically preventing or delaying the early engulfment stages of angiophagy, can improve
thromboembolic washout, and microvascular flow and viability, leading to better post-ischemic outcomes. We
aim to discover signaling pathways that regulate the various stages of endothelial plasticity involved in this
process, with the goal of identifying potential therapeutic targets. We will use an innovative multidisciplinary
approach to elucidate these mechanisms including mutant mice, pharmacological manipulations and high
resolution intravital imaging of occluded microvessels. Additionally, we will test our candidate drugs in a
translational model of transient ischemic stroke. These studies are likely to advance our understanding of
mechanisms of microvascular occlusion and recanalization and could identify novel targets to prevent the no-
reflow phenomenon in stroke and other ischemic conditions.

## Key facts

- **NIH application ID:** 10134455
- **Project number:** 5R01NS111961-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jaime Grutzendler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,092
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134455

## Citation

> US National Institutes of Health, RePORTER application 10134455, Therapeutic targeting of angiophagy to achieve microvascular recanalization (5R01NS111961-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134455. Licensed CC0.

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