# Mechanisms and clinical relevance of hypercapnia-induced skeletal muscle atrophy in Chronic Obstructive Pulmonary Disease (COPD)

> **NIH NIH K01** · ALBANY MEDICAL COLLEGE · 2021 · $61,776

## Abstract

Project Summary: Patients with chronic obstructive pulmonary disease (COPD)/pulmonary emphysema often
develop locomotor muscle dysfunction, which is associated with worse clinical outcomes including higher
mortality. Retention of CO2 in the blood, or hypercapnia, is also frequent in these patients and similarly associated
with higher mortality. The mechanisms that regulate these processes are currently unknown, and the available
treatments have no effects on survival in this setting. Therefore, understanding the mechanisms controlling CO2-
retaining COPD-driven muscle dysfunction could help develop strategies to prevent and reverse that, with
potentially survival and quality of life benefits for these patients. Muscle dysfunction in COPD is associated with
abnormal protein turnover and metabolism. The present extension proposes to investigate the contribution of
dysregulated cellular metabolism to the pathophysiology of CO2-retaining COPD. The hypothesis that supports
this application is that hypercapnia attenuates COPD-induced reduced fiber respiration via LKB1-AMPK-driven
mitochondrial biogenesis. To investigate that hypothesis, we will determine the specific mechanisms that
regulate CO2-driven dysfunctional metabolism. As LKB1/AMPK controls CO2 sensing and protein turnover in
skeletal muscle, hypercapnia’s effect on metabolism will be investigated with LKB1 knockout cells exposed to
elevated CO2. This research represents a substantive departure from the status quo by focusing on the
contribution of metabolism to the long-term effects of COPD-driven muscle dysfunction, and specifically by
identifying AMPK as major players COPD muscle respiration and function.

## Key facts

- **NIH application ID:** 10395661
- **Project number:** 3K01HL130704-05S1
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Adolfo Ariel Jaitovich
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $61,776
- **Award type:** 3
- **Project period:** 2016-07-15 → 2022-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395661

## Citation

> US National Institutes of Health, RePORTER application 10395661, Mechanisms and clinical relevance of hypercapnia-induced skeletal muscle atrophy in Chronic Obstructive Pulmonary Disease (COPD) (3K01HL130704-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10395661. Licensed CC0.

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