10 research outputs found
Identification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity
BACKGROUND: Lipid metabolism in mammals is orchestrated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs) that control the expression of genes required for the uptake and synthesis of cholesterol, fatty acids, and triglycerides. SREBPs are thus essential for insulin-induced lipogenesis and for cellular membrane homeostasis and biogenesis. Although multiple players have been identified that control the expression and activation of SREBPs, gaps remain in our understanding of how SREBPs are coordinated with other physiological pathways.
METHODOLOGY: To identify novel regulators of SREBPs, we performed a genome-wide cDNA over-expression screen to identify proteins that might modulate the transcription of a luciferase gene driven from an SREBP-specific promoter. The results were verified through secondary biological assays and expression data were analyzed by a novel application of the Gene Set Enrichment Analysis (GSEA) method.
CONCLUSIONS/SIGNIFICANCE: We screened 10,000 different cDNAs and identified a number of genes and pathways that have previously not been implicated in SREBP control and cellular cholesterol homeostasis. These findings further our understanding of lipid biology and should lead to new insights into lipid associated disorders
Surgical aortic valvuloplasty and decalcification using the cavitron ultrasonic surgical aspirator: Long-term hemodynamic and angiographic followup
Surgical aortic valvuloplasty and decalcification using the cavitron ultrasonic surgical aspirator: Long-term hemodynamic and angiographic followup
Intravascular ultrasound versus digital subtraction angiography: A human in vivo comparison of vessel size and morphology
Balloon angioplasty of coarctation of the aorta evaluated with intravascular ultrasound imaging
Ergonovine maleate testing during cardiac catheterization: A 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina
Central Sympathetic Inhibition Augments Sleep-Related Ultradian Rhythm of Parasympathetic Tone in Patients With Chronic Heart Failure
Therapeutic strategies targeting connexins
The connexin family of channel-forming proteins is present in every tissue type in the human anatomy. Connexins are best known for forming clustered intercellular channels, structurally known as gap junctions, where they serve to exchange members of the metabolome between adjacent cells. In their single-membrane hemichannel form, connexins can act as conduits for the passage of small molecules in autocrine and paracrine signalling. Here, we review the roles of connexins in health and disease, focusing on the potential of connexins as therapeutic targets in acquired and inherited diseases as well as wound repair, while highlighting the associated clinical challenges