# Nocturnal hypoxemia dysregulates skeletal muscle protein homeostasis in COPD

> **NIH HL K08** · CLEVELAND CLINIC LERNER COM-CWRU · 2026 · $151,578

## Abstract

Chronic obstructive pulmonary disease (COPD) is the 4th most common cause of death in the United States.
Sarcopenia, or skeletal muscle loss, impacts up to 40% of COPD patients and is a major cause of morbidity
and mortality. Despite the high significance, there are currently no effective therapies for sarcopenia in COPD
due to limited understanding of the underlying mechanisms of skeletal muscle loss. However, we have
identified that nocturnal hypoxemia, or low oxygen saturation during sleep and normal oxygen saturation while
awake, is associated with sarcopenia in COPD patients. Nocturnal hypoxemia causes tissue-level hypoxia in
the skeletal muscle, a condition we have termed prolonged intermittent hypoxia (PIH). Our preliminary and
published data indicate that PIH upregulates hypoxia inducible factor (HIF)1α-dependent gene targets whose
products dysregulate important muscle signaling and metabolic pathways to cause sarcopenia. These findings
support the hypothesis that PIH induces HIF1α activity in skeletal muscle leading to sarcopenia in COPD. This
hypothesis will be tested in vitro and in vivo in two specific AIMS. In Aim 1, we will determine the role of HIF1α
on key aspects of skeletal muscle protein synthesis and homeostasis in response to PIH in vitro using
loss/gain of HIF1α in murine myotubes and primary muscle cultures from murine and human models. In Aim 2,
we will determine the role of HIF1α on key aspects of skeletal muscle protein synthesis, homeostasis and
muscle function in response to PIH in live mice ± experimentally induced COPD ± PIH ± muscle specific
deletion of HIF1α. Our proposal is innovative in concept because our novel model of PIH is a clinically relevant
model that COPD patients routinely experience and is associated with sarcopenia. Our studies have the
potential for broad application and high clinical relevance because PIH occurs in other pulmonary disorders
associated with sarcopenia, such as interstitial lung disease or pulmonary hyp

## Key facts

- **NIH application ID:** 11251655
- **Project number:** 5K08HL168348-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** AMY  ATTAWAY
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $151,578
- **Award type:** 5
- **Project period:** 2025-01-01T00:00:00 → 2029-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11251655

## Citation

> US National Institutes of Health, RePORTER application 11251655, Nocturnal hypoxemia dysregulates skeletal muscle protein homeostasis in COPD (5K08HL168348-02). Retrieved via AI Analytics 2026-07-15 from https://api.ai-analytics.org/grant/nih/11251655. Licensed CC0.

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