# Epigenetic and Transcriptional Regulation of Angiogenic Regulator CD36 and Transformation of Capillaries into Small Arteries

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $371,250

## Abstract

Project Summary
Arteriolar differentiation and formation of small arteries from very tiny blood vessels (capillary arterialization)
are fundamental processes underlying ischemic organ recovery from a noxious insult. Despite its obvious
clinical and biological importance, little is known about the molecular mechanisms of these events and their
regulation. We have recently discovered that transcriptional repression of CD36 is involved in a proangiogenic
and proarteriogenic reprogramming of capillary endothelial cells (EC) or microvascular EC (MVECs), and is
implicated in capillary arterialization. Specifically, we have shown that LPA/PKD-1 signaling-mediated CD36
transcriptional repression plays a key role in promoting arteriogenic gene expression in MVECs, and
microvascular remodeling in vivo. Moreover, EC-specific deletion of pkd-1 showed impaired recovery from
ischemic insult. These unexpected findings led to the hypothesis that CD36 gene repression via LPA/PKD-1
signaling axis reprograms MVECs to differentiate into arteriolar ECs and promotes capillary arterialization. To
test this hypothesis, we have established two- and three-dimensional MVEC culture systems, and in vivo
Matrigel assays. More importantly, we have established hindlimb ischemia models in unique cd36 gene
deficient mice with the EC-specific translating ribosome affinity purification (TRAP), and EC-specific pkd-1
deficient mice or EC-specific pkd-1 deficient TRAP mice. These novel TRAP transgenic lines have targeted
gene deficiency and carry an EC-specific EGFP-tag that allows us to directly purify ribosome-bound mRNA
from ECs in vivo for next generation RNA-sequencing, facilitating probes of EC-specific transcriptome and
ribosome binding of noncoding RNAs. The availability of this mouse model provides us for the first time with
the ability to devise experiments to gain new and fundamental insights into biology of adult arteriolar growth
under ischemic conditions. Using these tools,, we aim to 1) prove that in MVECs the LPA/PKD-1-CD36
signaling axis is essential to regulate MVEC reprogramming and arteriolar differentiation; 2) test the hypothesis
that CD36 transcriptional repression via the LPA/PKD-1-FoxO1 signaling axis is a critical component of a
genetic reprogramming switch to promote capillary arterialization (de novo arteriogenesis). Together with
assays using a series of molecular biology and imaging methods single cell RNA-sequencing as well as
zebrafish models, we expect to accomplish these aims and provide a comprehensive evaluation of arteriolar
differentiation and capillary arterialization. This will illuminate poorly explored and poorly understood aspects of
vascular biology. This proposal focuses on de novo arteriogenesis in adult because of its remarkably practical
significance. Getting a greater understanding of capillary arterialization in adult tissues will provide important
insights into finding novel and effective therapeutic targets against ischemic heart and...

## Key facts

- **NIH application ID:** 9868321
- **Project number:** 5R01HL136423-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** BIN Ren
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868321

## Citation

> US National Institutes of Health, RePORTER application 9868321, Epigenetic and Transcriptional Regulation of Angiogenic Regulator CD36 and Transformation of Capillaries into Small Arteries (5R01HL136423-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868321. Licensed CC0.

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