Autophagic flux is increased in peripheral blood mononuclear cells in atherosclerotic vascular disease and associates inversely with adverse cardiovascular events
- 14. School of Medicine, College of Health, Adelaide University, Adelaide, SA 5000, Australia; 5. Vascular Research Centre, Lifelong Health Theme, South Australia
Abstract
Background: Autophagy is a homeostatic pathway supporting stress adaptation and is dysregulated in atherosclerosis. Its potential as a biomarker or therapeutic target in atherosclerotic vascular disease (ASVD) remains incompletely defined. We measured autophagic flux in peripheral blood mononuclear cells (PBMCs) from patients with peripheral arterial disease (PAD) or carotid stenosis (CS), compared with healthy controls, and explored clinical outcome associations. Methods: Ninety-four patients with PAD or CS and 19 healthy controls were studied. Autophagic flux was quantified from fresh blood using a validated ex vivo chloroquine inhibition ELISA measuring LC3BII accumulation. Major adverse cardiovascular events (MACE) and major adverse limb events (MALE) were ascertained over a median follow up of 828 days. Results: The ASVD cohort comprised claudication (n = 16), chronic limb threatening ischemia (CLTI; n = 49), and CS (n = 29). Autophagic flux was higher in ASVD than controls (mean 281.4 vs. 182.3 ng LC3BII/mg protein/h; p < 0.0001) and remained independently associated after multivariable adjustment. Within CLTI, concurrent infection was associated with lower flux (p = 0.001), approaching control levels (p = 0.327). In CLTI, higher flux quartiles were associated with lower MACE risk, most strongly for quartile 3 (hazard ratio 0.07 vs. quartile 1, 95% CI 0.01 to 0.50; p = 0.009). Conclusion: Autophagic flux is elevated in PBMCs from ASVD patients, independent of age and sex. Attenuated flux in CLTI with concurrent infection may indicate autophagic exhaustion in advanced disease. The association between higher flux and lower MACE in CLTI suggests prognostic utility, warranting evaluation in larger prospective studies.
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BibTeX
@misc{beelders2026autophagic,
title = {{Autophagic flux is increased in peripheral blood mononuclear cells in atherosclerotic vascular disease and associates inversely with adverse cardiovascular events}},
author = {B. Beelders and L. K. Hein and N. Wattchow and M. T. Nguyen and S. Torabiardakani and T. Salagaras and S. Liyanage and C. A. Bursill and R. Fitridge and N. McMillan and C. L. Delaney and T. J. Sargeant and P. J. Psaltis},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753342},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753342v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Autophagic flux is increased in peripheral blood mononuclear cells in atherosclerotic vascular disease and associates inversely with adverse cardiovascular events
AU - B. Beelders
AU - L. K. Hein
AU - N. Wattchow
AU - M. T. Nguyen
AU - S. Torabiardakani
AU - T. Salagaras
AU - S. Liyanage
AU - C. A. Bursill
AU - R. Fitridge
AU - N. McMillan
AU - C. L. Delaney
AU - T. J. Sargeant
AU - P. J. Psaltis
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753342
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753342v1
AB - Background: Autophagy is a homeostatic pathway supporting stress adaptation and is dysregulated in atherosclerosis. Its potential as a biomarker or therapeutic target in atherosclerotic vascular disease (ASVD) remains incompletely defined. We measured autophagic flux in peripheral blood mononuclear cells (PBMCs) from patients with peripheral arterial disease (PAD) or carotid stenosis (CS), compared with healthy controls, and explored clinical outcome associations. Methods: Ninety-four patients with PAD or CS and 19 healthy controls were studied. Autophagic flux was quantified from fresh blood using a validated ex vivo chloroquine inhibition ELISA measuring LC3BII accumulation. Major adverse cardiovascular events (MACE) and major adverse limb events (MALE) were ascertained over a median follow up of 828 days. Results: The ASVD cohort comprised claudication (n = 16), chronic limb threatening ischemia (CLTI; n = 49), and CS (n = 29). Autophagic flux was higher in ASVD than controls (mean 281.4 vs. 182.3 ng LC3BII/mg protein/h; p < 0.0001) and remained independently associated after multivariable adjustment. Within CLTI, concurrent infection was associated with lower flux (p = 0.001), approaching control levels (p = 0.327). In CLTI, higher flux quartiles were associated with lower MACE risk, most strongly for quartile 3 (hazard ratio 0.07 vs. quartile 1, 95% CI 0.01 to 0.50; p = 0.009). Conclusion: Autophagic flux is elevated in PBMCs from ASVD patients, independent of age and sex. Attenuated flux in CLTI with concurrent infection may indicate autophagic exhaustion in advanced disease. The association between higher flux and lower MACE in CLTI suggests prognostic utility, warranting evaluation in larger prospective studies.
ER -