# Ingrid Fleming

**Ingrid Fleming** is a biochemist and vascular pharmacologist who directs the Institute for Vascular Signalling at [Goethe University Frankfurt](https://www.edgepedia.org/goethe-university-frankfurt). Her research concerns how endothelial cells, the cells lining blood vessels, signal to one another and to the vessel wall, with a particular focus on cytochrome P450-derived lipid mediators and the soluble epoxide hydrolase (sEH) enzyme in diabetes.<sup>[1](https://www.mdc-berlin.de/system/files/events/c00ef410-9b65-11eb-9049-4fa6ee2b02f9-cv-fleming.pdf)</sup><sup> • </sup><sup>[2](https://www.uni-frankfurt.de/151067115/Institute_for_Vascular_Signalling?)</sup> Her listed fields of scholarship include cytochrome P450 and soluble epoxide hydrolase, nitric oxide synthases, lipid mediator signaling, platelet reactivity, and the vascular complications of diabetes.<sup>[3](https://www.ae-info.org/ae/Member/Fleming_Ingrid)</sup>

| Key fact | Detail |
|---|---|
| Position | Professor of Physiology (W3) and Director of the Institute for Vascular Signalling, Goethe University Frankfurt |
| Field | Vascular signaling; endothelial biology; lipid mediators in diabetes<sup>[2](https://www.uni-frankfurt.de/151067115/Institute_for_Vascular_Signalling?)</sup> |
| Signature work | "Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy", *Nature*, 2017<sup>[4](https://www.nature.com/articles/nature25013)</sup> |
| Honours |  |<sup>[3](https://www.ae-info.org/ae/Member/Fleming_Ingrid)</sup><sup> • </sup><sup>[5](https://jung-stiftung.de/wp-content/uploads/2022/05/Press-release_Jung-Foundation_Laureates-2022_Ingrid-Fleming.pdf)</sup>

## Career

She moved to Germany for a postdoctoral position at the Institute of Applied Physiology, Albert-Ludwigs-University Freiburg, from 1991 to 1993.<sup>[1](https://www.mdc-berlin.de/system/files/events/c00ef410-9b65-11eb-9049-4fa6ee2b02f9-cv-fleming.pdf)</sup> She was a group leader from 1999 to 2004 and full professor of physiology from 2004 to 2008; since 2008 she has held the Chair for Vascular Signalling and directed the Institute for Vascular Signalling, and since 2010 she has also chaired the Centre for Molecular Medicine.<sup>[1](https://www.mdc-berlin.de/system/files/events/c00ef410-9b65-11eb-9049-4fa6ee2b02f9-cv-fleming.pdf)</sup><sup> • </sup><sup>[3](https://www.ae-info.org/ae/Member/Fleming_Ingrid)</sup>

Her institute studies the biology of the vascular wall and heart, including mediators that endothelial cells generate themselves: nitric oxide, hydrogen sulfide, and products of cytochrome P450 enzymes and the soluble epoxide hydrolase, with a translational emphasis on cardiovascular therapy.<sup>[2](https://www.uni-frankfurt.de/151067115/Institute_for_Vascular_Signalling?)</sup> She became vice dean for research of the Goethe University faculty of medicine and co-speaker of the Collaborative Research Centre CRC 1531 "Damage control by the stroma-vascular fraction".<sup>[6](https://ivs-frankfurt.de/id-fleming-copy/)</sup> 

## Endothelium-derived hyperpolarizing factor and nitric oxide signaling

Endothelium-derived hyperpolarizing factor (EDHF) is a name for the signals by which endothelial cells hyperpolarize and relax vascular smooth muscle independently of nitric oxide. Its chemical identity was long disputed: proposed mediators have included epoxyeicosatrienoic acids (EETs), potassium ion, hydrogen peroxide, [C-type natriuretic peptide](https://www.edgepedia.org/c-type-natriuretic-peptide), and anandamide, and EDHF activity is represented by different chemicals in different vascular beds and species.<sup>[7](https://www.ahajournals.org/doi/full/10.1161/01.HYP.0000255173.50317.fc)</sup> A 1999 *Nature* paper identified a cytochrome P450 enzyme, CYP2C, as an EDHF synthase in coronary arteries, giving one branch of this pathway a specific molecular source.<sup>[8](https://doi.org/10.1016/s1050-1738(00)00065-7)</sup> Cytochrome P450 epoxygenases metabolize arachidonic acid into EETs, which open calcium-activated potassium channels, hyperpolarize the membrane and relax vascular smooth muscle.<sup>[7](https://www.ahajournals.org/doi/full/10.1161/01.HYP.0000255173.50317.fc)</sup>

Two *Circulation Research* papers in 2001 extended this work. The first, a 2001 [Circulation Research](https://www.edgepedia.org/circulation-research) paper first-authored by Fleming, showed that the EDHF synthase CYP2C9 is itself a functionally significant source of reactive oxygen species in coronary arteries, so the same enzyme can contribute to oxidative stress as well as to hyperpolarization.<sup>[9](https://www.ahajournals.org/doi/full/10.1161/01.RES.88.1.44)</sup> Fleming's later reviews connect these threads: CYP-derived EETs act as an EDHF and influence angiogenic and inflammatory signaling, and the epoxygenases also metabolize the omega-3 fatty acids EPA and DHA into bioactive epoxides that can be more potent than EETs, while sEH inhibition raises epoxide levels with anti-hypertensive and anti-inflammatory effects.<sup>[10](https://pubmed.ncbi.nlm.nih.gov/26975734/)</sup>

## Soluble epoxide hydrolase and diabetic retinopathy

The soluble epoxide hydrolase converts CYP-generated epoxides into fatty acid diols, high concentrations of which have vascular destabilizing effects; the epoxides themselves are generally protective, anti-inflammatory, and insulin-sensitizing.<sup>[11](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00739/full)</sup>

**Representative work.** The 2017 *Nature* paper [Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy](https://doi.org/10.1038/nature25013) identified sEH as a key enzyme initiating pericyte (cell wrapping capillaries, keeping them stable) loss and breakdown of the endothelial barrier in diabetic retinopathy, by generating the diol 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) from docosahexaenoic acid.<sup>[4](https://www.nature.com/articles/nature25013)</sup> The mechanism is structural: the diol acts on the cell membrane to alter the localization of cholesterol-binding proteins and interferes with the association of presenilin 1 with N-cadherin and VE-cadherin, weakening both pericyte–endothelial contacts and the junctions between endothelial cells.<sup>[4](https://www.nature.com/articles/nature25013)</sup>

The evidence included human tissue, not only animals: sEH expression and 19,20-DHDP accumulation were increased in diabetic mouse retinas and in the retinas and vitreous humor of patients with diabetes, using vitreous samples from over a dozen patients undergoing vitrectomy for proliferative diabetic retinopathy.<sup>[4](https://www.nature.com/articles/nature25013)</sup><sup> • </sup><sup>[12](https://escholarship.org/content/qt1jz047s6/qt1jz047s6.pdf)</sup> In the Ins2<sup>Akita</sup> mouse model, the sEH inhibitor t-AUCB, given from 6 weeks to 12 months of age, significantly reduced 19,20-DHDP production and lessened pericyte loss, acellular capillaries, and vascular permeability. Conversely, overexpressing sEH in retinal Müller glial cells of non-diabetic mice produced vascular abnormalities within 14 days, which an sEH inhibitor abolished.<sup>[12](https://escholarship.org/content/qt1jz047s6/qt1jz047s6.pdf)</sup> Fleming and co-authors filed patent applications, German no. 10 2016 109 709.8 and international PCT/EP2017/062618, for the use of sEH inhibitors against non-proliferative diabetic retinopathy.<sup>[4](https://www.nature.com/articles/nature25013)</sup>

## How it compares with other approaches

Current treatments for diabetic retinopathy, pan-retinal photocoagulation, anti-VEGF injections, and vitreoretinal surgery, address late-stage disease. Fleming's 2019 review states that anti-VEGF therapy and laser photocoagulation treat the symptoms of late-stage retinal disease but that no treatment is available that prevents disease progression, and a 2022 review notes that not all patients respond to these methods and that treatments for early diabetic retinopathy remain lacking.<sup>[11](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00739/full)</sup><sup> • </sup><sup>[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC9180978/)</sup> sEH inhibition differs in targeting an upstream metabolic step, preventing the formation of a vessel-destabilizing diol rather than blocking VEGF downstream.<sup>[11](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00739/full)</sup>

The picture is not simple. A later study reported that sEH knockout potentiated diabetes-induced retinal damage by promoting VEGF while reducing the tight-junction proteins ZO-1 and occludin, and cited the finding that rising EETs in retinal endothelial cells, as well as 19,20-DHDP accumulation in Müller glial cells, can contribute to retinopathy; it proposed combining EET blockade with an AT1 receptor blocker.<sup>[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC7728430/)</sup> This suggests that the balance between protective epoxides and damaging diols, and between cell types in the retina, determines the outcome of manipulating the pathway.<sup>[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC9180978/)</sup><sup> • </sup><sup>[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC7728430/)</sup>

## Representative work

- **"Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy"**, *Nature* (2017), [doi:10.1038/nature25013](https://doi.org/10.1038/nature25013).

## Honors and roles

Her honors include the 1999 Servier Research Prize and the Heinz Meise-Preis of the German Heart Foundation, the 2000 Nitric Oxide Society Young Investigator Award, the 2002 Arthur Weber Prize of the German Cardiac Society and the 2003 Schunk-Preis for Medicine.<sup>[1](https://www.mdc-berlin.de/system/files/events/c00ef410-9b65-11eb-9049-4fa6ee2b02f9-cv-fleming.pdf)</sup><sup> • </sup><sup>[3](https://www.ae-info.org/ae/Member/Fleming_Ingrid)</sup> In 2022 she was a Jung Foundation laureate for work on preventing the secondary complications of diabetes, having identified a specific lipid mediator responsible for diabetic retinopathy and investigated drug-based approaches against it.<sup>[5](https://jung-stiftung.de/wp-content/uploads/2022/05/Press-release_Jung-Foundation_Laureates-2022_Ingrid-Fleming.pdf)</sup>

## Recent developments

Since 2023 Fleming has held a [German Research Foundation](https://www.edgepedia.org/german-research-foundation) (DFG) grant titled "Deciphering the role of soluble epoxide hydrolase in homeostasis with Chemical Biology tools"; according to the Institute for Vascular Signalling, she has been co-speaker of CRC 1531 since 2022, alongside her longer-running collaborative projects in the [Frankfurt](https://www.edgepedia.org/frankfurt) center.<sup>[6](https://ivs-frankfurt.de/id-fleming-copy/)</sup> A 2022 review in the field states that only clinical trials could establish whether sEH inhibition prevents or treats microvascular type 2 diabetes complications, and that such trials are still needed.<sup>[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC9180978/)</sup>

## References

1. [Curriculum Vitae: Fleming, Ingrid Professor Dr.](https://www.mdc-berlin.de/system/files/events/c00ef410-9b65-11eb-9049-4fa6ee2b02f9-cv-fleming.pdf)
2. [Goethe-Universität, Institute for Vascular Signalling](https://www.uni-frankfurt.de/151067115/Institute_for_Vascular_Signalling?)
3. [Academy of Europe: Fleming Ingrid](https://www.ae-info.org/ae/Member/Fleming_Ingrid)
4. [Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy (Nature, 2017)](https://www.nature.com/articles/nature25013)
5. [Jung Foundation Laureates 2022, Ingrid Fleming (press release)](https://jung-stiftung.de/wp-content/uploads/2022/05/Press-release_Jung-Foundation_Laureates-2022_Ingrid-Fleming.pdf)
6. [ID Fleming – Institute for Vascular Signalling](https://ivs-frankfurt.de/id-fleming-copy/)
7. [Arachidonic Acid Metabolites as Endothelium-Derived Hyperpolarizing Factors (Hypertension)](https://www.ahajournals.org/doi/full/10.1161/01.HYP.0000255173.50317.fc)
8. https://doi.org/10.1016/s1050-1738(00)00065-7
9. [Endothelium-Derived Hyperpolarizing Factor Synthase (Cytochrome P450 2C9) Is a Functionally Significant Source of Reactive Oxygen Species in Coronary Arteries](https://www.ahajournals.org/doi/full/10.1161/01.RES.88.1.44)
10. [The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling (Vascular Pharmacology, 2016)](https://pubmed.ncbi.nlm.nih.gov/26975734/)
11. [New Lipid Mediators in Retinal Angiogenesis and Retinopathy (Frontiers in Pharmacology, 2019)](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00739/full)
12. [Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy (author manuscript)](https://escholarship.org/content/qt1jz047s6/qt1jz047s6.pdf)
13. [Soluble Epoxide Hydrolase and Diabetes Complications (review)](https://pmc.ncbi.nlm.nih.gov/articles/PMC9180978/)
14. [A novel interaction between soluble epoxide hydrolase and the AT1 receptor in retinal microvascular damage](https://pmc.ncbi.nlm.nih.gov/articles/PMC7728430/)

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*Topic: Encyclopedia › Life and health › Life and health scientists › Medical and health researchers › Researchers in cardiovascular, metabolic, and endocrine research*

*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 15, 2026 · Last review: Sep 25, 2026*

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