@Article{biocell.2025.069272,
AUTHOR = {Eduard Belskikh, Yuliya Marsyanova, Denis Melnikov, Oleg Uryasev, Valentina Zvyagina},
TITLE = {Endothelial and Mitochondrial Dysfunction in COPD Pathophysiology: Focus on Homocysteine–L-Carnitine Interplay},
JOURNAL = {BIOCELL},
VOLUME = {49},
YEAR = {2025},
NUMBER = {11},
PAGES = {2093--2123},
URL = {http://www.techscience.com/biocell/v49n11/64544},
ISSN = {1667-5746},
ABSTRACT = {Elevated homocysteine is a clinically relevant metabolic signal in chronic obstructive pulmonary disease (COPD). Higher circulating levels track with oxidative stress, endothelial dysfunction, mitochondrial impairment, and pulmonary vascular remodeling, rise with disease severity, and may contribute to the excess cardiovascular risk—although effect sizes and causality remain uncertain. This review centers on the homocysteine–carnitine relationship in COPD pathophysiology. Carnitine deficiency, prevalent in COPD, can worsen mitochondrial bioenergetics, promote accumulation of acyl intermediates, and reduce nitric oxide bioavailability via endothelial nitric oxide synthase uncoupling (eNOS). Conversely, restoring carnitine status in experimental and early clinical settings has been associated with lower homocysteine, improved nitric oxide signaling, and attenuation of vascular remodeling, suggesting a reciprocal link rather than a one-way pathway. We review existing evidence on various COPD phenotypes and severities, delineate mechanisms that connect homocysteine, carnitine metabolism, mitochondria, redox balance and eNOS uncoupling, and evaluate therapeutic strategies—ranging from lowering homocysteine with B-group vitamins to integrated approaches that also support mitochondrial function and redox homeostasis, including targeted carnitine supplementation. The role of L-carnitine as a potential therapeutic agent for lowering homocysteine and improving mitochondrial and vascular function warrants further investigation, as it may help slow the progression of COPD and its related comorbidities.},
DOI = {10.32604/biocell.2025.069272}
}