To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19% ) and stroke volume (31% ) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 ,Im2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted. (J. Clin. Invest 1995. 95:619-627.) Key words: insulin-like growth factor-i * cardiac hypertrophy . left ventricular remodeling -myocardial cell size -collagen
A novel ferrocenium capped amphiphilic pillar[5]arene (FCAP) was synthesized and self-assembled to cationic vesicles in aqueous solution. The cationic vesicles, displaying low cytotoxicity and significant redox-responsive behavior due to the redox equilibrium between ferrocenium cations and ferrocenyl groups, allow building an ideal glutathione (GSH)-responsive drug/siRNA co-delivery system for rapid drug release and gene transfection in cancer cells in which higher GSH concentration exists. This is the first report of redox-responsive vesicles assembled from pillararenes for drug/siRNA co-delivery; besides enhancing the bioavailability of drugs for cancer cells and reducing the adverse side effects for normal cells, these systems can also overcome the drug resistance of cancer cells. This work presents a good example of rational design for an effective stimuli-responsive drug/siRNA co-delivery system.
Extracellular vesicles, including microvesicles and exosomes, are lipidic membrane‐derived vesicles that are secreted by most cell types. Exosomes, one class of these vesicles that are 30–100 nm in diameter, hold a great deal of promise in disease diagnostics, as they display the same protein biomarkers as their originating cell. For exosomes to become useful in disease diagnostics, and as burgeoning drug delivery platforms, they must be isolated efficiently and effectively without compromising their structure. Most current exosome isolation methods have practical problems including being too time‐consuming and labor intensive, destructive to the exosomes, or too costly for use in clinical settings. To this end, this study examines the use of poly(ethylene terephthalate) (PET) capillary‐channeled polymer (C‐CP) fibers in a hydrophobic interaction chromatography (HIC) protocol to isolate exosomes from diverse matrices of practical concern. Initial results demonstrate the ability to isolate extracellular vesicles enriched in exosomes with comparable yields and size distributions on a much faster time scale when compared to traditional isolation methods. As a demonstration of the potential analytical utility of the approach, extracellular vesicle recoveries from cell culture milieu and a mock urine matrix are presented. The potential for scalable separations covering submilliliter spin‐down columns to the preparative scale is anticipated.
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