# Role of TLR2 in angiogenesis

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $639,696

## Abstract

ABSTRACT.
Emerging clinical importance of innate immunity and Toll-like receptors (TLRs) in vascular development and
diseases, and discoveries of new endogenous TLRs ligands generated by lipid oxidation and their expanding
functions in human pathologies underscore importance of TLRs (TLR2 in particular) in cardiovascular and lung
diseases and vascular pathologies associated with inflammation, such as retinal diseases of aging and diabetes.
TLR2 expression is not restricted to immune system; it is functional on other cells, including endothelium and
can be activated by bacterial and endogenous ligands, i.e. products of lipid peroxidation. The knowledge of
endothelial TLR2 is limited to studies with inhibitors or ubiquitous TLR2 KO. Accordingly, we propose to establish
a role for endothelial TLR2 in angiogenesis using postnatal and developmental models. We will test that
endothelial TLR2 regulates angiogenesis by two mechanisms: directly by integrin-mediated migration and
indirectly, by promoting recruitment of myeloid cells. TLR2-dependent angiogenesis is augmented in the
presence of exogenous bacterial TLR2 ligands as well as endogenous TLR2 ligands, i.e. CEP, especially in
tissues where its endogenous ligand is highly prevalent (i.e. in retinas). Our specific Aims are: Aim 1. To define
the cell autonomous function of TLR2 on endothelium by using endothelial-specific (Cdh5-CreERT) KO mice in
postnatal (wound, tumors) models and developmental (retinal) angiogenesis. Aim 2. To assess the role of TLR2-
dependent myeloid cells recruitment in angiogenesis. To establish the role of EC TLR2 as we as the role of
myeloid TLR2 using KO (CX3CR1-CreERT) in myeloid cells recruitment during postnatal and developmental
angiogenesis. Aim 3. To define the proangiogenic pathways activated by endogenous and exogenousTLR2
ligands in endothelial cells. The regulatory function and mechanism of TLR2/CD36 complex will be addressed.
Role for TLR2/Myd88/TIRAP/IRAK3/4/TRAF6 and Src family kinases in regulation of proangiogenic integrin
functions, i.e. activation, adhesion and migration will be established. Main targets of TLR2 pathway novel to EC
biology, e.g. TRAF6 will be verified in vivo using novel reagents. These studies will establish for the first time a
direct role of endothelial TLR2 in angiogenesis and will link innate immunity and vascularization, especially in
pathologies associated and exacerbated by infection, inflammation and oxidative stress.

## Key facts

- **NIH application ID:** 9858408
- **Project number:** 5R01HL145536-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Tatiana V Byzova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $639,696
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858408

## Citation

> US National Institutes of Health, RePORTER application 9858408, Role of TLR2 in angiogenesis (5R01HL145536-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858408. Licensed CC0.

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