# Regulation of Arterial Function by Apelin/APJ Receptor Mechanisms

> **NIH NIH R15** · NORTH DAKOTA STATE UNIVERSITY · 2020 · $435,000

## Abstract

Mechanisms linking obesity and hypertension to ischemic heart disease (IHD) are not clearly understood.
Most patients with IHD suffer from atherosclerotic lesions that limit coronary blood flow; however, more than
one-third of all patients have no observable obstruction on angiography. The flow-limiting reductions in
coronary arterial diameter in such patients are thought to be due to functional abnormalities (i.e. enhanced
vasoconstriction; impaired vasodilation). Apelin is formed in adipose tissue and secreted into the circulation
where it has multiple effects on blood vessel function, depending on the vascular bed. Activation of the
apelin/APJ receptor-signaling pathway has vasodilatory effects in important vascular beds (e.g. pulmonary)
and is generally thought to play a protective role in the cardiovascular system. Our long-term goal is to
understand the mechanisms by which apelin regulates vasomotor tone in health and disease. Studies from
our lab indicate that apelin causes endothelium- and NO-dependent relaxation of healthy coronary arteries.
By contrast, in coronary arteries from hypertensive animals we found that apelin failed to cause arterial
relaxation and, instead, inhibited endothelium-dependent relaxation to acetylcholine. Our central hypothesis
is that the apelin/APJ receptor axis does not provide a protective vasodilator role in the coronary circulation
in hypertension, but rather presents a net vasoconstrictor activity in this vascular bed. It is further
hypothesized, based on strong preliminary data, that this adverse effect of apelin is due to inhibition of NO
production in hypertensive coronary endothelial cells. It is proposed that the apelin-mediated inhibition of
NO synthesis in hypertensive coronary arteries is sufficient to functionally impair the arteries and create a
local environment that favors vasoconstriction. This is significant, as it would predictably increase the risk of
coronary vascular dysfunction in conditions with elevated plasma apelin levels, such as obesity. Two
specific aims are designed to investigate our hypotheses: In Aim #1, we will address the hypothesis that the
distinction between the effect of apelin in normotensive vs hypertensive coronary arteries is secondary to
changes in APJ receptor levels or location within the vessel wall. Quantitative measurements of gene and
protein expression, as well as imaging studies to determine the spatial localization of APJ receptors in the
coronary arterial wall will be used to accomplish this aim. In Aim #2, a combination of molecular biological,
functional, and imaging techniques will be used to identify which signaling pathway(s) coupling APJ receptor
activation to NO production is disrupted in hypertensive coronary arteries. The knowledge gained from
these studies will have strong positive impact by increasing our understanding of the mechanisms that
control coronary vasomotor tone under hypertensive conditions. Such information may provide new targets
f...

## Key facts

- **NIH application ID:** 9964297
- **Project number:** 2R15HL124338-02A1
- **Recipient organization:** NORTH DAKOTA STATE UNIVERSITY
- **Principal Investigator:** Chengwen Sun
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $435,000
- **Award type:** 2
- **Project period:** 2020-04-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964297

## Citation

> US National Institutes of Health, RePORTER application 9964297, Regulation of Arterial Function by Apelin/APJ Receptor Mechanisms (2R15HL124338-02A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9964297. Licensed CC0.

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