No abstract

Adenovirus-mediated transfer of COX-1 to angioplasty-injured carotid arteries was efficacious in augmenting PGI2 synthesis and was associated with an inhibition of thrombosis when a relatively high titer of adenovirus was instilled.

Background:The regulation of CDCA8 gene expression remains unclear. Results: CDCA8 promoter is activated in hESCs and cancer cells, in which NF-Y is a positive-regulator by binding to the CCAAT-box. Conclusion: CDCA8 is transcriptionally activated in hESCs and cancer cells and is positively regulated by NF-Y. Significance: Characterization of CDCA8 regulation provides a better understanding of its biological functions.

Previous studies have shown that gene therapy with inducible nitric oxide synthase (iNOS) protects against myocardial infarction at 3 days after gene transfer. However, the long-term effects of iNOS gene therapy on myocardial ischemic injury and cardiac function are unknown. To address this issue, we used a recombinant adenovirus 5 (Ad5) vector (Av3) with deletions of the E1, E2a, and E3 regions, which enables long-lasting recombinant gene expression for at least 2 mo due to lack of inflammation. Mice received intramyocardial injections in the left ventricular (LV) anterior wall of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 1 or 2 mo later, they were subjected to myocardial infarction (30-min coronary occlusion followed by 4 h of reperfusion). Cardiac iNOS gene expression was confirmed by immunoblotting and activity assays at 1 and 2 mo after gene transfer. In the iNOS group, infarct size (percentage of risk region) was significantly reduced (P < 0.05) both at 1 mo (24.2 ± 3.4%, n = 6, vs. 48.0 ± 3.6%, n = 8, in the LacZ group) and at 2 mo (23.4 ± 3.1%, n = 8, vs. 36.6 ± 2.4%, n = 7). The infarct-sparing effects of iNOS gene therapy were as powerful as those observed 24 h after ischemic preconditioning (23.1 ± 3.4%, n = 10). iNOS gene transfer had no effect on LV function or dimensions up to 8 wk later (echocardiography). These data demonstrate that iNOS gene therapy mediated by the Av3 vector affords long-term (2 mo) cardioprotection without inflammation or adverse functional consequences, a finding that provides a rationale for further preclinical testing of this therapy. Keywordsnitric oxide synthase; cardiac function; mouse Although ischemic preconditioning (PC) is known to be a powerful cardioprotective adaptation, it has not yet found clinical application. The late phase of PC would appear particularly suitable for therapeutic exploitation because it is underlain by the upregulation of cardioprotective genes, which, if expressed chronically, could conceivably induce a longlasting PC state (3, 4). Among these genes, the inducible isoform of nitric oxide (NO) synthase (iNOS) has been studied most thoroughly. Extensive evidence over the past decade demonstrates that iNOS is an obligatory mediator of the protection afforded by late PC induced by various stimuli, including ischemia, physical exercise, and various pharmacological agents (1-3, 5). Therefore, upregulation of iNOS appears to be a final common pathway whereby diverse stimuli induce a shift of the heart to a defensive clinically to protect the ischemic myocardium, it is important to determine whether chronic overexpression of iNOS in the myocardium is cardioprotective.In this regard, a number of experimental and clinical results have been interpreted to suggest that enhanced production of NO via iNOS is detrimental to the myocardium (13,20). Increased iNOS activity has been reported in ventricular tissue from patients with dilated cardiomyopathy (6). Increased iNOS activity has also been found in myocarditis, ischemic heart disease, valv...

No abstract