Selective TNF-α targeting with Infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter

MARCHINI T; D'ANNUNZIO V; PAZ ML; CACERES L; GARCES M; PEREZ V; TASAT D; VANASCO V; MAGNANI N; GONZALEZ MAGLIO D; GELPI RJ; ALVAREZ S; EVELSON P

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: BETHESDA; Año: 2015 vol. 309 p. 1621 - 1628

0363-6135

ABSTRACTInflammation plays a central role in the onset and progression ofcardiovascular diseases associated with the exposure to air pollutionparticulate 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 i.p. injection of Infliximab (10 mg/kg body weight) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body weight). 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 and lusitropic reserve were evaluated according to the Langendorff technique.ROFA instillationinduced a significantdecrease intissueO2 consumptionand active mitochondrial respiration by 32% and 31%, respectively, in comparison with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2consumption, and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice.Moreover, Infliximab-pretreated ROFA-exposed mice showed conserved LVDP and cardiac O2consumption 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.NEW & NOTEWORTHYThe present study shows that impaired cardiacO2 metabolism and ventricular function in response to  adrenergic stimulus following an acute exposure to air pollution particulate matter can be attenuated by blocking TNF-α-dependent systemic inflammation with Infliximab, and emphasizes the importance of environmental factors and inflammation in cardiovascular disease.