Cardiac phenotype in -related syndromes: A multicenter cohort study.

Objective: To define the risks and consequences of cardiac abnormalities in -related syndromes.

Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an knock-in mouse (Mashl) to determine the sequence of events in seizure-related cardiac death.

Knockout of the X-linked in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity.

Fibroblast growth factor (FGF)13, a nonsecreted, X-linked, FGF homologous factor, is differentially expressed in adipocytes in response to diet, yet 's role in metabolism has not been explored. Heterozygous knockouts fed normal chow and housed at 22°C showed hyperactivity accompanying reduced core temperature and obesity when housed at 30°C. Those heterozygous knockouts showed defects in thermogenesis even at 30°C and an inability to protect core temperature.

Inducible ablation enhances caveolae-mediated cardioprotection during cardiac pressure overload.

The fibroblast growth factor (FGF) homologous factor FGF13, a noncanonical FGF, has been best characterized as a voltage-gated Na channel auxiliary subunit. Other cellular functions have been suggested, but not explored. In inducible, cardiac-specific knockout mice, we found-even in the context of the expected reduction in Na channel current-an unanticipated protection from the maladaptive hypertrophic response to pressure overload.

FGF13 modulates the gating properties of the cardiac sodium channel Na1.5 in an isoform-specific manner.

FGF13 (FHF2), the major fibroblast growth factor homologous factor (FHF) in rodent heart, directly binds to the C-terminus of the main cardiac sodium channel, Na1.5. Knockdown of FGF13 in cardiomyocytes induces slowed ventricular conduction by altering Na1.

Cyclosporine up-regulates Krüppel-like factor-4 (KLF4) in vascular smooth muscle cells and drives phenotypic modulation in vivo.

Cyclosporine A (CSA, calcineurin inhibitor) has been shown to block both vascular smooth muscle cell (VSMC) proliferation in cell culture and vessel neointimal formation following injury in vivo. The purpose of this study was to determine molecular and pathological effects of CSA on VSMCs. Using real-time reverse transcription-polymerase chain reaction, Western blot analysis, and immunofluorescence microscopy, we show that CSA up-regulated the expression of Krüppel-like factor-4 (KLF4) in VSMCs.