Involvement of the Early Growth Response Protein 1 in Vascular Pathophysiology: An Overview.

Hyperactivation of proliferative and growth promoting pathways underlies the progression of vessel remodeling, leading to vascular dysfunction. An upregulation of early growth response protein 1 (Egr-1), a zinc finger transcription factor has been observed in several models of vascular diseases. In the vasculature, Egr-1 expression can be induced by multiple hormonal, metabolic and external stimuli, such as growth factors, cytokines, reactive oxygen species, hyperglycaemia and stretch-induced stress. The structure of the Egr-1 promoter allows both its auto-regulation and its binding with several regulatory transcription cofactors like the serum response factor and the cAMP response element binding protein. Pharmacological and genetic studies have revealed the involvement of several signaling pathways that contribute to the expression of Egr-1. Among them, the mitogen-activated protein kinase pathway has emerged as a predominant signaling cascade that regulates Egr-1 transcription in response to various stimuli. Moreover, targeted deletion of Egr-1 by DNAzymes, antisense oligonucleotides or RNA interference has also helped in defining the importance of Egr-1 in the pathophysiology of vascular diseases. Neointimal formation and expression of genes directly linked with proinflammatory processes have been demonstrated to be enhanced by Egr-1 expression and activity. This review provides an overview on the signaling components implicated in Egr-1 expression and discusses its potential involvement in vascular pathophysiology.

Reunión clínica inter-hospitales: síndrome antifosfolípidos catastrófico, un cuadro de microangiopatía / Catastrophic antiphospholipid syndrome, a case of microangiopathy

Se presenta el caso de una mujer joven, sin antecedentes de importancia, que muestra trombosis de grandes y pequeños vasos. A pesar del tratamiento con anticoagulación y corticoides en dosis altas, desarrolla necrosis cutánea y una importante respuesta inflamatoria sistémica con disfunción orgánica múltiple, por lo que .se le indicó plasmaféresis y, posteriormente, rituximab, con buena respuesta. Se discute el síndrome antifosfolípidos con énfasis en los anticuerpos antiprotrombina y la patogenia de la microangiopatía en el síndrome antifosfolípidos catastróficos.

We present the case of a young, otherwise healthy woman, who developed thrombosis of large and small vessels and capillaries. Despite anticoagulation treatment and high doses of glucocorticoids, she developed cutaneous necrosis and systemic inflammatory response with multiple organ dysfunction. Plasmapheresis and rituximab were administered with good response. We discuss the antiphospholipid syndrome, with emphasis on antiprothrombin antibodies and the pathogenesis of microangiopathy in antiphospholipid syndrome.