Background-Increasing evidence supports the role of heme oxygenase-1 (HO-1) in cytoprotective response and iron homeostasis. The object of this study was to investigate whether adenovirus-mediated gene transfer of HO-1 in arteries reduces iron overload and inhibits lesion formation in apolipoprotein E (apoE)-deficient mice. Methods and Results-Infection of rat aortic smooth muscle cells with adenovirus carrying the human HO-1 gene (Adv-HO-1) resulted in a high-level expression of HO-1 protein, which effectively reduced the hemin-induced iron overload in these cells. Adenovirus-mediated gene transfer in arteries in vivo was achieved by direct injection of Adv-HO-1 into the left ventricles of anesthetized animals. Transgene was expressed in the endothelium and aortic lesion of apoE-deficient mice after they had received recombinant adenovirus for 1 week and gradually decayed during the next 5 weeks. When young apoE-deficient mice (14 weeks old) received Adv-HO-1 (2.5ϫ10 9 pfu) for 6 weeks, lesions that developed in the aortic root or aortic arch were significantly smaller than those in control littermates receiving empty viral vector. Furthermore, the iron deposition as well as tissue iron content was much less in aortic tissue of Adv-HO-1-treated mice. The inhibitory effect of HO-1 gene transfer on the progression of advanced lesions was also observed in older apoE-deficient mice (20 weeks old) receiving Adv-HO-1 intraventricularly. Conclusions-Overexpression

Our results suggest that Adv-bcl-xL gene transfer significantly improves ischemia/reperfusion-induced renal dysfunction via the downregulation of renal tubular apoptosis and autophagy.

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TRPV1 activation in ECs may trigger Ca(2+)-dependent PI3K/Akt/CaMKII signalling, which leads to enhanced phosphorylation of TRPV1, increased TRPV1-eNOS complex formation, eNOS activation and, ultimately, NO production.

Objective-Brain expresses abundant lipocalin-type prostaglandin (PG) D 2 (PGD 2 ) synthase but the role of PGD 2 and its metabolite, 15-deoxy-⌬ 12,14 PGJ 2 (15d-PGJ 2 ) in brain protection is unclear. The aim of this study is to assess the effect of 15d-PGJ 2 on neuroprotection. Methods and Results-Adenoviral transfer of cyclooxygenase-1 (Adv-COX-1) was used to amplify the production of 15d-PGJ 2 in ischemic cortex in a rat focal infarction model. Cortical 15d-PGJ 2 in Adv-COX-1-treated rats was increased by 3-fold over control, which was correlated with reduced infarct volume and activated caspase 3, and increased peroxisome proliferator activated receptor-␥ (PPAR␥) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d-PGJ 2 resulted in reduction of infarct volume, which was abrogated by a PPAR␥ inhibitor. Rosiglitazone infusion had a similar effect. 15d-PGJ 2 and rosiglitazone at low concentrations suppressed H 2 O 2 -induced rat or human neuronal apoptosis and necrosis and induced PPAR␥ and HO-1 expression. The anti-apoptotic effect was abrogated by PPAR␥ inhibition. Key Words: COX-1 Ⅲ 15d-PGJ 2 Ⅲ PPAR␥ Ⅲ apoptosis Ⅲ stroke P rostaglandin (PG) H synthase-1 (also known as cyclooxygenase-1 [COX-1]) is constitutively expressed in almost all mammalian cells. 1 It is a bifunctional enzyme with a cyclooxygenase activity that converts arachidonic acid to PG G 2 (PGG 2 ) and a peroxidase activity that converts PGG 2 to PGH 2 . 2 PGH 2 is converted to diverse prostanoids by specific enzymes. COX-1 plays an important role in maintaining physiological homeostasis and protecting brain tissues from ischemia-reperfusion (I/R) injury. COX-1 deleted mice are highly susceptible to ischemic brain infarction, 3 whereas COX-1 overexpression protects brain from I/R damage, which is abrogated by a selective COX-1 inhibitor. 4 COX-1 overexpression in ischemic brain augments the production of PGI 2 , PGD 2 , and PGE 2 , and suppresses leukotriene B 4 (LTB 4 ) and LTC 4 . As LTB 4 and LTC 4 have been shown to be detrimental to brain tissue, whereas PGI 2 is protective, 5-7 COX-1 overexpression tilts the eicosanoid balance toward tissue protection. PGD 2 is elevated in COX-1 overexpressed brain tissues but its role in brain I/R injury is unclear. Brain is enriched in lipocalin-type PGD synthase (L-PGDS), which catalyzes the formation of abundant PGD 2 . 8 The role of PGD 2 in I/R brain injury is unclear. As 15-deoxy-⌬ 12,14 ; PGJ 2 (15d-PGJ 2 ), a nonenzymatic product of PGD 2 , was shown to possess anti-inflammatory properties through activation of peroxisome proliferator activated receptor-␥ (PPAR␥), 9 -13 PGD 2 has been implicated in tissue protection. However, it has recently been argued that the tissue 15d-PGJ 2 level is too low to elicit an anti-inflammatory action in vivo, especially in vascular tissues. 14 In view of abundant expression of L-PGDS and PGD 2 in brain, we postulated that 15d-PGJ 2 contributes to cerebral protection. Our experimental findings show a considerable amount of 15d-PGJ 2 in ischemia brain, which...