# Vascular endothelial dysfunction in sleep apnea

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $714,783

## Abstract

Abstract
Obstructive sleep apnea (OSA), a highly prevalent condition, triples the risk for cardiovascular disease.
Observational studies suggested that continuous positive airway pressure (CPAP) therapy improves
cardiovascular outcomes in OSA. However, 3 recent randomized clinical trials failed to confirm those findings,
indicating that cardiovascular risk persists in OSA despite effective elimination of intermittent hypoxia (IH). Our
preliminary data suggest that CPAP may unexpectedly exacerbate the pro-inflammatory milieu in OSA, which
may contribute to the residual cardiovascular risk observed in randomized trials of CPAP therapy. Thus,
alternative therapies for OSA-related cardiovascular risk are urgently needed. Using endothelial cells (ECs)
freshly harvested from OSA patients, we identified increased deposition of the complement membrane attack
complex (MAC) on ECs, a consequence of increased internalization of the complement inhibitor CD59 from the
EC surface, as a trigger of endothelial inflammation in OSA. We showed that this process is mediated by
alterations in EC cholesterol metabolism and trafficking in response to IH and is blocked by statins. We found
that randomly allocated statin therapy protects ECs from MAC-induced inflammation compared to placebo,
including in OSA patients adherent with CPAP. In the same study, CPAP had no impact on MAC deposition.
Unlike CPAP, statins do not eliminate IH episodes in OSA. However, by lowering systemic and cellular
cholesterol levels, statins may exert endothelial protection by inhibiting complement-mediated vascular injury in
OSA, suggesting a novel therapeutic strategy that may allow OSA patients to continue to benefit from CPAP-
mediated elimination of IH and fragmented sleep while reducing their cardiovascular risk. Statin use among OSA
patients has been consistently low: only 8-13% of OSA patients are prescribed statins in studies spanning the
last decade, indicating that this potentially beneficial therapy has been vastly underutilized in OSA patients. We
will use rigorous randomized, double blind, parallel group, placebo controlled study design and ECs
harvested from otherwise healthy OSA patients to assess the overall hypothesis that statins stabilize
endothelial function by improving endothelial cholesterol metabolism and trafficking regardless of the adherence
with CPAP therapy. To address this overall hypothesis, we will determine 1) whether statins reduce endothelial
inflammation and pro-thrombotic conditions in OSA, including in patients adherent to CPAP who may express
increased inflammatory markers (Aim 1), and 2) whether statins reduce endothelial inflammation and pro-
thrombotic conditions by improving endothelial cholesterol metabolism and trafficking in OSA (Aim 2). These
studies will advance our understanding of the mechanisms underlying endothelial dysfunction and cardiovascular
risk in OSA that seem to persist despite effective CPAP therapy. Since a minority of OSA patient...

## Key facts

- **NIH application ID:** 10367416
- **Project number:** 2R01HL106041-09
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sanja Jelic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $714,783
- **Award type:** 2
- **Project period:** 2011-06-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367416

## Citation

> US National Institutes of Health, RePORTER application 10367416, Vascular endothelial dysfunction in sleep apnea (2R01HL106041-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10367416. Licensed CC0.

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