Heparin modulates the expression of genes encoding pro and anti-apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats

Abstract

PURPOSE:To investigate if expression of genes encoding pro and anti-apoptotic proteins in the rat enteric endothelial cells stimulated by intestinal ischemia followed by reperfusion (IR) can be modified by treatment with heparin (HP). METHODS:Eighteen adult Wistar rats were divided in three groups: sham group submitted to laparotomy only (SG), ischemia followed by reperfusion group (IRG); ischemia followed by reperfusion plus pretreatment with HP 100 mg.kg -1 (IRG+HP). Ischemia was performed by clamping of the superior mesenteric artery. After 60 min of ischemia, metal clamps were removed for reperfusion for 120 min. Gene expression of encoding pro (Casp1, Casp6, Casp3, Cflar, Fas and Pgl) and anti-apoptotic (Bcl2, Bcl2l1 and Naip2) proteins in rat enteric endothelial cells was evaluated by PCR microarray method. RESULTS:Compared to rat endothelial cells of SG, the expression of pro-apoptotic genes was up-regulated in IRG while anti-apoptotic genes were down-regulated. In contrast, the expression of anti-apoptotic genes in IRG+HP was up-regulated while pro-apoptotic genes was down-regulated compared to SG. CONCLUSION:The attenuation by heparin of intestinal ischemia-reperfusion previously demonstrated in rodents could be related with ability of this drug to stimulate and reduce gene expression of encoding anti and pro-apoptotic proteins, respectively.

Therapeutic targeting of extracellular DNA improves the outcome of intestinal ischemic reperfusion injury in neonatal rats

“…Heparin is best recognized for its ability to prevent blood coagulation by catalytically accelerating the interaction of antithrombin III with thrombin and factors XIIa, IXa, Vlla, Xa, thereby inhibiting the proteases necessary for completion of the coagulation cascade. In particular, enoxaparin has been shown to have beneficial effects on neutrophil recruitment, oxidative stress, apoptosis and tissue damage, as reported in previous studies 45 – 47 . In comparison to enoxaparin, alteplase with its fibrinolytic activity, binds to an already formed thrombus and catalyzes the conversion of plasminogen to plasmin.…”

Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis

“…Interestingly, ENX was able to markedly lower cardiac tissue levels of caspase-3 in DOX-treated rats, suggesting a considerable potential for ENX therapy to modulate cellular apoptosis and therefore alter the course of DOX-mediated cardiac cell death. The exact mechanism by which ENX contributes reductions in caspase-3 in DOX-induced cardiotoxicity has not been determined; however, the anti-apoptotic effect of heparins has been clearly demonstrated in previous studies and been attributed to reductions in the expression of pro-apoptotic proteins such as caspase-3, B-cell lymphoma 2-associated X protein (Bax), apoptosis stimulating fragment (Fas) and stimulation of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) [ 55 , 56 ]. These effects are thought to be promoted by various cellular actions including free radical scavenging activity and/or suppression of the inflammatory response [ 56 ].…”

“…The exact mechanism by which ENX contributes reductions in caspase-3 in DOX-induced cardiotoxicity has not been determined; however, the anti-apoptotic effect of heparins has been clearly demonstrated in previous studies and been attributed to reductions in the expression of pro-apoptotic proteins such as caspase-3, B-cell lymphoma 2-associated X protein (Bax), apoptosis stimulating fragment (Fas) and stimulation of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) [ 55 , 56 ]. These effects are thought to be promoted by various cellular actions including free radical scavenging activity and/or suppression of the inflammatory response [ 56 ]. Taken together, it is therefore possible that our observation of ENX-mediated decreases in the inflammatory mediators, TNF-α and IL-1β, and the partial improvement in the antioxidant capacity of cardiac tissue may have underlined reductions in DOX-mediated increases in cellular caspase-3 level.…”

MicroRNA‐351‐5p aggravates intestinal ischaemia/reperfusion injury through the targeting of MAPK13 and Sirtuin‐6

“…The damage was slightly reduced when the times of reoxygenation and reperfusion were longer than 60 and 90 min respectively. As mentioned earlier, oxidative stress, inflammation and apoptosis play important roles in the occurrence and development of intestinal I/R (Pope et al, 2010;Pantazi et al, 2013;Taha et al, 2014). ROS and TUNEL staining are often used to evaluate oxidative stress and apoptosis.…”