RESUMEN
Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD.
Asunto(s)
Ácido Araquidónico/metabolismo , Ácidos Araquidónicos/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Ácido 8,11,14-Eicosatrienoico/sangre , Adulto , Anciano , Ácidos Araquidónicos/sangre , Biomarcadores/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Sistema Enzimático del Citocromo P-450/sangre , Femenino , Humanos , Ácidos Hidroxieicosatetraenoicos/sangre , Inflamación/sangre , Inflamación/metabolismo , Masculino , Metabolómica , Persona de Mediana EdadRESUMEN
Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus-infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended.