ABSTRACT
PURPOSE OF REVIEW: Sleep disorders represent a significant comorbidity in the heart failure population, and there is mounting evidence that treatment of sleep disorders such as obstructive sleep apnea can significantly improve cardiac function. However, the link between these two disorders is still not entirely clear. RECENT FINDINGS: Recently, a novel neurohormonal pathway has been elucidated involving signaling molecules now collectively known as the orexins, which have been implicated in regulating autonomic function during sleep/wake cycles. Further evidence has mounted that orexin signaling is deeply perturbed in the setting of sleep disorders, and furthermore that abnormal orexin signaling may be implicated in the pathology of heart failure. The orexin signaling pathway represents an enticing novel target for both the treatment of sleep disorders as well as heart failure, and may represent one facet of the "missing link" between these two prevalent and often comorbid diseases.
Subject(s)
Heart Failure/epidemiology , Orexins/physiology , Sleep Wake Disorders/epidemiology , Sleep/physiology , Comorbidity , Heart Failure/etiology , Humans , Sleep Wake Disorders/metabolismABSTRACT
The Bmp2 3'untranslated region (UTR) sequence bears a sequence conserved between mammals and fishes that can post-transcriptionally activate or repress protein synthesis. We developed a map of embryonic cells in the mouse where this potent Bmp2 regulatory sequence functions by using a lacZ reporter transgene with a 3'UTR bearing two loxP sites flanking the ultra-conserved sequence. Cre-recombinase-mediated deletion of the ultra-conserved sequence caused strong ectopic expression in proepicardium, epicardium and epicardium-derived cells (EPDC) and in tissues with known epicardial contributions (coronary vessels and valves). Transient transfections of reporters in the epicardial/mesothelial cell (EMC) line confirmed this repression. Ectopic expression of the recombined transgene also occurred in the aorta, outlet septum, posterior cardiac plexus, cardiac and extracardiac nerves and neural ganglia. Bmp2 is dynamically regulated in the developing heart. 3'UTR-mediated mechanisms that restrain BMP2 synthesis may be relevant to congenital heart and vasculature malformations and to adult diseases involving aberrant BMP2 synthesis.
Subject(s)
Bone Morphogenetic Protein 2/metabolism , Heart/physiology , Pericardium/metabolism , 3' Untranslated Regions , Animals , Bone Morphogenetic Protein 2/genetics , Cell Line , Conserved Sequence , Embryo, Mammalian/cytology , Embryo, Mammalian/metabolism , Embryo, Mammalian/physiology , Embryonic Development , Gene Expression Regulation, Developmental , Genes, Reporter , Heart/embryology , Heart/innervation , Immunohistochemistry , Integrases/metabolism , Lac Operon , Mice , Mice, Inbred C57BL , Mice, Transgenic/genetics , Mice, Transgenic/metabolism , Neurofilament Proteins/genetics , Neurofilament Proteins/metabolism , Pericardium/cytology , Pericardium/embryology , Pericardium/physiology , Protein Processing, Post-Translational , Rats , Regulatory Sequences, Nucleic Acid , Sequence Deletion , Transcription, Genetic , Transfection , TransgenesABSTRACT
Incontinentia pigmenti is a rare X-linked genodermatosis that affects mainly female neonates. Skin manifestations are the most common and occur in four quite distinct phases. A female infant presented vesiculobullous lesions on trunk and limbs, and a verrucous lesion on the right palm. Biopsy revealed eosinophil exocytosis and pigment incontinence, confirming the clinical hypothesis. Although uncommon, incontinentia pigmenti should be taken into consideration as a possible differential diagnosis when vesiculobullous and verrucous lesions are present in childhood.
Subject(s)
Genetic Diseases, X-Linked/diagnosis , Incontinentia Pigmenti/diagnosis , Female , Humans , InfantABSTRACT
A incontinência pigmentar é uma genodermatose rara, ligada ao X, que afeta, principalmente, neonatos do sexo feminino. As manifestações cutâneas são as mais prevalentes, e ocorrem em quatro fases bem distintas. Lactente feminina com lesões vesicobolhosas em tronco e membros e lesão verrucosa em palma. À biopsia, observou-se exocitose eosinofílica e derrame pigmentar, compatível com a suspeita clínica. Apesar de incomum, a incontinência pigmentar deve ser lembrada entre os diagnósticos diferenciais, de lesões vesicobolhosas e verrucosas da infância.
Incontinentia pigmenti is a rare X-linked genodermatosis that affects mainly female neonates. Skin manifestations are the most common and occur in four quite distinct phases. A female infant presented vesiculobullous lesions on trunk and limbs, and a verrucous lesion on the right palm. Biopsy revealed eosinophil exocytosis and pigment incontinence, confirming the clinical hypothesis. Although uncommon, incontinentia pigmenti should be taken into consideration as a possible differential diagnosis when vesiculobullous and verrucous lesions are present in childhood.