RT info:eu-repo/semantics/article
T1 Metformin: Experimental and clinical evidence for a potential role in emphysema treatment.
A1 Córdoba Lanús, Aída Elizabeth
A1 Polverino, Francesca
A1 David Wu, Tianshi
A1 Rojas- Quintero, Joselyn
A1 Wang, Xiaoyun
A1 Mayo, Jonathan
A1 Tomchaney, Michael
A1 Tram, Judy
A1 Packard, Samuel
A1 Zhang, Duo
A1 Cleveland, Kristan H.
A1 Owen, Caroline A.
A1 Fawzy, Ashraf
A1 Kinney, Greg L.
A1 Hersh, Craig P
A1 Zmijewsk, Jaroslaw
A1 Konhilas, John
A1 Langlais, Paul R.
A1 Schnellmann, Rick
A1 Rahman, Irfan
A1 McCormack, Meredith
A1 Celli, Bartolome
A1 Casanova, Ciro
A2 Medicina InternaDermatología y Psiquiatría
K1 aging
K1 comorbidities
K1 metformin
K1 cigarette smoke
K1 chronic obstructive pulmonary disease
AB Rationale: Cigarette smoke (CS) inhalation triggers oxidative stressand inflammation, leading to accelerated lung aging, apoptosis, andemphysema, as well as systemic pathologies. Metformin is beneficialfor protecting against aging-related diseases.Objectives: We sought to investigate whether metformin mayameliorate CS-induced pathologies of emphysematous chronicobstructive pulmonary disease (COPD).Methods: Mice were exposed chronically to CS and fed metforminenriched chow for the second half of exposure. Lung, kidney, and musclepathologies, lung proteostasis, endoplasmic reticulum (ER) stress,mitochondrial function, and mediators of metformin effectsin vivo and/orin vitrowere studied. We evaluated the association of metformin usewith indices of emphysema progression over 5 years of follow-up amongthe COPDGene (Genetic Epidemiology of COPD) study participants.The association of metformin use with the percentage of emphysemaand adjusted lung density was estimated by using a linear mixed model.Measurements and Main Results: Metformin protected againstCS-induced pulmonary inflammation and airspace enlargement; smallairway remodeling, glomerular shrinkage, oxidative stress, apoptosis,telomere damage, aging, dysmetabolism in vivo and in vitro; and ERstress. The AMPK (AMP-activated protein kinase) pathway wascentral to metformin’s protective action. Within COPDGene,participants receiving metformin compared with those not receiving ithad a slower progression of emphysema (20.92%; 95% confidenceinterval [CI], 21.7% to 20.14%; P= 0.02) and a slower adjusted lungdensity decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P= 0.01).Conclusions: Metformin protected against CS-induced lung, renal,and muscle injury; mitochondrial dysfunction; and unfolded proteinresponses and ER stress in mice. In humans, metformin use wasassociated with lesser emphysema progression over time. Our resultsprovide a rationale for clinical trials testing the efficacy of metforminin limiting emphysema progression and its systemic consequences.
YR 2021
FD 2021
LK http://riull.ull.es/xmlui/handle/915/41310
UL http://riull.ull.es/xmlui/handle/915/41310
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 13-abr-2025