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OBJECTIVES: Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning. METHODS: Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured. RESULTS: Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. CONCLUSION: The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and (3) recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF-1α, miR-21 and miR-210 expression.

Increasing evidence indicates that inflammation plays an important role in intimal hyperplasia (IH) induced by autologous vein grafts. The proteasome inhibitor bortezomib shows anti-inflammatory effects, so we used an autologous vein transplantation model to test whether bortezomib inhibits neointimal formation in transplant-induced vasculopathy.We subjected 88 rats to autologous external jugular vein grafting surgery randomly assigned to be treated with bortezomib or vehicle. After 24 or 72 hours, rats were humanely killed and vein grafts processed for real-time RT-PCR (24 and 72 hours), ELISA (24 hours), or neutrophil chemotaxis assay (24 hours). Subsequently, rats were humanely killed at 1 and 2 weeks after grafting with samples processed for morphometric analysis.Bortezomib significantly inhibited IH at 2 weeks compared with untreated controls (P.05). Expression of mRNA for vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant 2beta, monocyte chemoattractant-1, interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha markedly increased in injured vessels during the first day after surgery declining over the following 3 days. Bortezomib significantly attenuated gene expression and protein levels of most inflammatory mediators (P.05), simultaneously inhibiting neutrophil chemotactic activity of vessel homogenates.Bortezomib inhibited neointimal formation at least partially by attenuating the inflammatory response in transplant-induced vasculopathy. It may become a novel vasoprotective agent in the clinical field.

Olmesartan, as a new angiotensin II receptor blocker, has shown beneficial effects on cardiovascular diseases. Nevertheless, the effect of olmesartan on ischemia/reperfusion (I/R) injury in the hypertensive heart has not been investigated. Therefore, the present study aimed to investigate the effect of olmesartan on I/R injury in spontaneously hypertensive rats (SHRs). Experimental groups were designed with a 2×2 factorial design for olmesartan and I/R effects. In the I/R group, the left anterior descending coronary artery (LAD) was ligated for 40 min followed by a 180-min reperfusion. In the sham group, SHRs underwent the same surgical procedure as the I/R group, with the exception that the suture passed under the LAD without being tightened. In the Olm-I/R group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the I/R group. In the Olm-sham group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the sham group. Infarct size was measured for the I/R and Olm-I/R groups. Blood pressure (BP), serum creatine kinase (CK), left ventricular mass index (LVMI), high mobility group box 1 (HMGB1) protein expression levels and hypoxia-inducible factor-1α (HIF-1α) mRNA expression levels were measured for all four groups. Olmesartan significantly reduced BP and LVMI in the olmesartan-treated SHRs compared with those in the SHRs that were not treated with olmesartan. HMGB1 and HIF-1α expression levels were significantly decreased in the Olm-sham and Olm-I/R groups compared with those in the sham and I/R groups, respectively. The proportional increase in HIF-1α expression due to I/R was greater in the olmesartan-treated rats than in the untreated rats. Serum CK levels were significantly reduced in the Olm-I/R group compared with those in the I/R group. In conclusion, olmesartan ameliorates left ventricular hypotrophy and protects the heart against I/R injury in addition to lowing BP in SHRs. The protective effect of olmesartan may be partly due to its antioxidative and anti-inflammatory properties.

OBJECTIVES: Internal mammary arteries graft failure in coronary artery bypass grafting (CABG) is mostly considered to be a result of competitive flow (CF) from the native coronary artery, which significantly limits future revascularization options. METHODS: With the left internal mammary artery (LIMA) anastomosed to the left anterior descending (LAD) coronary artery using an off-pump technique, CABG was performed on 15 Chinese swine. Then we produced varying degrees of stenosis in the proximal LAD coronary artery with an adjustable flow occluder, measured the mean flow of the LIMA and LAD coronary artery and detected the plasma concentrations of nitric oxide (NO) and endothelin (ET) in the LIMA graft. RESULTS: When stenosis of the proximal LAD artery was decreased, the CF of the native LAD coronary artery showed an increasing trend, while the mean flow of the LIMA revealed a decreasing trend. Distal LAD coronary artery flow remained nearly constant, despite the varying proximal LAD artery or LIMA flow rates. An oscillating flow pattern (retrograde/antegrade) was noted in the LIMA graft when the proximal LAD coronary artery was not fully occluded. The plasma concentration of ET in the LIMA graft was significantly higher than that before grafting (P< 0.05), and the plasma concentration of NO was significantly lower (P< 0.05). The concentration of NO was positively related to the mean flow in the LIMA (r= 0.872, P< 0.05). CONCLUSIONS: CF from the native LAD coronary artery can decrease the blood flow in the LIMA graft and even change the direction of the flow. These changes may impair the function of the LIMA graft and affect ET or NO production, which in turn may lead to early LIMA graft failure.

[Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 45-year-old man with significant ST-segment changes in anterolateral derivations underwent cardiac catheterization. A coronary angiogram revealed severe stenosis and ectasia of