# Epigenetic Mechanisms of Developmental Regulation of Fetal, Newborn, and Adult Cerebral Artery Sympathetic Innervation and Alpha1 Adrenergic Receptor Subtypes

> **NIH NIH R01** · LOMA LINDA UNIVERSITY · 2021 · $395,000

## Abstract

Title: Epigenetic Mechanisms of Developmental Regulation of Fetal, Newborn, and Adult
Cerebral Artery Sympathetic Innervation and Alpha1 Adrenergic Receptor Subtypes
Project Summary: During the past half century there has been the rising rate of preterm birth
combined with a lowering of the age limit of viability. The premature fetus is more prone to
germinal matrix and other intracerebral hemorrhage, intraventricular hemorrhage, and related
problems as a consequence of stress during the process of birth. In contrast, the term-fetus is
able to autoregulate cerebral blood flow (CBF) despite the increase in systemic pressure and
minimize the occurrence of stress-induced hemorrhages. Recently, we have demonstrated that
lack of cerebral blood flow (CBF) autoregulation in the premature fetus is associated with
immaturity of the sympathetic (adrenergic) system. In concert with this, we also have
demonstrated that the adrenergic system undergoes a significant maturation with development.
In the proposed studies, we attempt to determine the mechanisms by which the premature fetus
can have greater cerebral autoregulation capability, as observed in the newborn lamb. In the
first three specific aims, ex-vivo, we will examine the role of DNA methylation, histone
modifications, microRNA, and lncRNA on the expression of the three alpha 1 adrenergic
receptor subtypes in premature fetus, near-term fetus, newborn lamb, and adult sheep. In the
fourth specific aim, in vivo, in the chronically catheterized preterm fetus, near-term fetus,
newborn lamb, and adult sheep, we will determine the effect of DNA methylation, histone
modifications, microRNAs, lncRNA, and alpha 1-adrenergic receptor subtypes in CBF regulation
with development in both the sexes. Overall, these studies will provide vital insights in the
sympathetic regulation of CBF with development, and suggest approaches to prevent or
ameliorate CBF dysregulation.

## Key facts

- **NIH application ID:** 10077333
- **Project number:** 5R01HL135786-47
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **Principal Investigator:** William J. Pearce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2016-12-09 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077333

## Citation

> US National Institutes of Health, RePORTER application 10077333, Epigenetic Mechanisms of Developmental Regulation of Fetal, Newborn, and Adult Cerebral Artery Sympathetic Innervation and Alpha1 Adrenergic Receptor Subtypes (5R01HL135786-47). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077333. Licensed CC0.

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