title: Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter.
abstract: Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality.
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Timoteo
authors.initials: T
authors.lastname: Marchini
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Verónica
authors.initials: V
authors.lastname: D'Annunzio
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; and.
authors.forename: Mariela L
authors.initials: ML
authors.lastname: Paz
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Lourdes
authors.initials: L
authors.lastname: Cáceres
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Mariana
authors.initials: M
authors.lastname: Garcés
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Virginia
authors.initials: V
authors.lastname: Perez
authors.affiliation: Escuela de Ciencia y Tecnología, Universidad Nacional de General San Martín, Buenos Aires, Argentina.
authors.forename: Deborah
authors.initials: D
authors.lastname: Tasat
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Virginia
authors.initials: V
authors.lastname: Vanasco
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Natalia
authors.initials: N
authors.lastname: Magnani
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez Maglio
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gelpi
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina;
authors.forename: Silvia
authors.initials: S
authors.lastname: Alvarez
authors.affiliation: Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; pevelson@ffyb.uba.ar.
authors.forename: Pablo
authors.initials: P
authors.lastname: Evelson
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D060729:Coal Ash / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation; D000069285:Infliximab / Q000494:pharmacology*; D000067268:Isolated Heart Preparation; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D052638:Particulate Matter / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000318:Adrenergic beta-Agonists; D018501:Antirheumatic Agents; D060729:Coal Ash; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D007545:Isoproterenol
keywords: air pollution; heart; inflammation; infliximab; residual oil fly ash