In this article, we explore the clinical and cellular phenomena of primary electrical diseases of the heart, that is, conditions purely related to ion channel dysfunction and not structural heart disease or reversible acquired causes. This growing classification of conditions, once considered together as "idiopathic ventricular fibrillation," continues to evolve and segregate into diseases that are phenotypically, molecularly, and genetically unique.
View Article and Find Full Text PDFPolymorphic ventricular tachycardia (PMVT) is an unusual ventricular tachyarrhythmia. Perhaps its most unique characteristic is a continuously evolving QRS morphology. Although the most common substrate for PMVT is structural heart disease, the prevalence of sudden cardiac death in the population without structural heart disease is even greater, and the absence of a myocardial substrate would suggest that PMVT is the anticipated cause of sudden cardiac death in this population as well.
View Article and Find Full Text PDFAngiotensin II via type 1 receptor activation upregulates the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and LOX-1 activation, in turn, upregulates angiotensin II type 1 receptor expression. We postulated that interruption of this positive feedback loop might attenuate the genesis of angiotensin II-induced hypertension and subsequent cardiac remodeling. To examine this postulate, LOX-1 knockout and wild-type mice were infused with angiotensin II or norepinephrine (control for angiotensin II) for 4 weeks.
View Article and Find Full Text PDFAims: Collagen, as a component of the extracellular matrix, has been linked to atherosclerotic plaque formation and stability. Activation of LOX-1, a lectin-like oxidized low-density lipoprotein (LDL) receptor-1, exerts a significant role in collagen formation. We examine the hypothesis that LOX-1 deletion may inhibit collagen accumulation in atherosclerotic arteries in LDL receptor (LDLR) knockout (KO) mice.
View Article and Find Full Text PDFLectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a receptor for oxidized-LDL, is up-regulated in activated endothelial cells, and it plays a role in atherothrombosis. However, its role in platelet aggregation is unclear. Both aspirin and HMG CoA reductase inhibitors (statins) reduce LOX-1 expression in endothelial cells.
View Article and Find Full Text PDFEven though non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for a long time, the search continues for anti-inflammatory drugs with few side-effects. COX-2 inhibitors are currently most debated, because they have less gastrointestinal side effects but have been linked to increased cardiovascular morbidity and mortality, presumably related to thrombotic events. This has brought about the withdrawal of rofecoxib and other COX-2 inhibitors from the market.
View Article and Find Full Text PDFLipid rafts accumulate in the immunological synapse formed by an organized assembly of the TCR/CD3, LFA-1, and signaling molecules. However, the precise role of lipid rafts in the formation of the immunological synapse is unclear. In this study, we show that LFA-1 on CTL is constitutively active and mediates Ag-independent binding of CTL to target cells expressing its ligands.
View Article and Find Full Text PDFMany surface receptors and signaling molecules are thought to associate with unique membrane microdomains termed lipid rafts. We examined the involvement of lipid rafts in the activation of leukocyte function-associated antigen-1 (LFA-1). Depletion or sequestration of cholesterol with methyl-beta-cyclodextrin (MCD) or filipin, respectively, strongly inhibited LFA-1-mediated adhesion of T-cell lines and primary T cells.
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