Background— The goal of this retrospective study was to determine the late outcome of surgical treatment for aortic valve regurgitation due to Takayasu arteritis and correlate it with evidence of inflammation on pathological examination. Methods and Results— Ninety consecutive patients who underwent surgery for aortic valve regurgitation due to Takayasu arteritis between 1979 and 2003 were studied. Intraoperative pathological specimens of the aortic wall from 69 patients were retrospectively examined for inflammation. Aortic valve replacement was performed in 63 patients (group A) and composite graft repair in 27 patients (group B). The aortic root diameter was 39.9±9.5 mm in group A and 54.4±13.6 mm in group B ( P <0.0001). Preoperative steroid therapy was performed in 40 patients (44.4%). Hospital mortality was 4.8% (3/63) in group A and 7.4% (2/27) in group B. The overall 15-year survival rate was 76.1%. Detachment of the valve or graft occurred in 11.1% (7/63) of group A and in 3.7% (1/27) of group B patients ( P =0.43). Late dilatation (>50 mm) of the residual ascending aorta occurred in 11.1% (7/63) of group A and in 3.7% (1/27) of group B patients ( P =0.43). Active inflammation was confirmed in intraoperative pathological specimens of 10 patients, and detachment of the valve or graft occurred in 4 of these patients. Univariate analysis of background variables revealed active inflammation to be a risk factor for detachment ( P =0.0001; risk ratio 55). Conclusions— Late dilatation of the ascending aorta after aortic valve replacement is a clinically important finding. Active inflammation could be related to valve or graft detachment.

Previously, we reported that a novel subpopulation of young mesenchymal stem cells (YMSCs) existed in old bone marrow, which possessed high antiaging properties as well as excellent efficacy for cardiac repair. MicroRNAs (miRNAs) have emerged as key regulators in posttranscriptional gene expression programs, and however, it is unknown whether miRNAs directly control stem cell senescence. Here we present the first evidence that miR-195 overexpressed in old MSCs (OMSCs) induces stem cell senescence deteriorating their regenerative ability by directly deactivating telomerase reverse transcriptase (Tert), and abrogation of miR-195 can reverse stem cell aging. MiRNAs profiling analysis in YMSCs and OMSCs by microarray showed that miR-140, miR-146a/b, and miR-195 were significantly upregulated in OMSCs, which led us to hypothesize that these are age-induced miRNAs involved in stem cell senescence. Of these miRNAs, we found SIGNIFICANCE STATEMENTIn this study, we investigated the role of miRNAs involved in stem cell aging and their impact on cardiac repair. Here we report our novel findings that regenerative ability of aged stem cells is deteriorated by increased expression of miR-195 which targets telomerase reverse transcriptase (Tert) gene, and abrogation of miR-195 in aged stem cells markedly induces Tert reactivation, resulting in significant telomere re-lengthening. Additionally, we show that transplantation of aged stem cells lacking miR-195 significantly reduced infarction size and concomitant improvement of cardiac function. These findings demonstrate that silencing miR-195 reverses the senescence clock in aged stem cells by telomerase reactivation. The strategy of modification of miRs in stem cells holds great promise for stem cell based repair of aging myocardium.

Despite recent advances in the carbonization of organic crystalline solids like metal-organic frameworks or supramolecular frameworks, it has been challenging to convert crystalline organic solids into ordered carbonaceous frameworks. Herein, we report a route to attaining such ordered frameworks via the carbonization of an organic crystal of a Ni-containing cyclic porphyrin dimer (Ni2-CPDPy). This dimer comprises two Ni–porphyrins linked by two butadiyne (diacetylene) moieties through phenyl groups. The Ni2-CPDPy crystal is thermally converted into a crystalline covalent-organic framework at 581 K and is further converted into ordered carbonaceous frameworks equipped with electrical conductivity by subsequent carbonization at 873–1073 K. In addition, the porphyrin’s Ni–N4 unit is also well retained and embedded in the final framework. The resulting ordered carbonaceous frameworks exhibit an intermediate structure, between organic-based frameworks and carbon materials, with advantageous electrocatalysis. This principle enables the chemical molecular-level structural design of three-dimensional carbonaceous frameworks.

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