裸金属支架置入术后再狭窄不是良性临床疾病

Background: Restenosis after percutaneous coronary intervention(PCI) has been thought to present in a stable manner as exertional angina. However, the presentation of in-stent restenosis(ISR) is not well-studied. We hypothesized that a substantial proportion of bare metal ISR presents as acute coronary syndromes. We aimed to characterize the severity of the clinical presentation of ISR. Methods: We searched our PCI database for all cases of PCI for bare metal ISR occurring between May 1999 and September 2003. Multivessel interventions were excluded. In-stent restenosis presentation was classified into three categories:(1) myocardial infarction(MI),(2) unstable angina requiring hospitalization before angiography, and(3) exertional angina. Routine angiographic screening after initial stent placement was not performed, so ISR episodes were clinical, rather than angiographic, ISR. Results: We identified 1186 cases of bare metal ISR in 984 patients. Median age was 63, 72%were male, and 36%had diabetes. Of the ISR episodes, 9.5%presented as acute MI(7.3%as non-ST-segment elevation MI and 2.2%as ST-segment elevation MI), 26.4%as unstable angina requiring hospitalization before angiography, and 64.1%as exertional angina. Conclusions: More than one third of bare metal ISR episodes presented as MI or unstable angina requiring hospitalization. The acuity of the clinical presentation of bare metal ISR appears to be more severe than has been previously thought. Aggressive efforts, such as drug-eluting stents to decrease the incidence of unstable angina due to bare metal ISR, are warranted.

Protein phosphatase 6 (Pp6) is crucial for regulatory T cell function and stability in autoimmunity

Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.