Cardioprotection from ischemia‐reperfusion injury due to Ras‐GTPase inhibition is attenuated by glibenclamide in the globally ischemic heart

Al-Rashdan, Ibrahim; Canatan, Halit; Al‐Maghrebi, May; Yousif, Mariam H. M.; Khan, Shah Alam; Benter, İbrahim F.

doi:10.1002/cbf.1353

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…Likewise, LVEDP, a marker of myocardial performance, is the pressure at the end of the filling phase of the heart. Increased LVEDP indicates an increased preload or incomplete emptying of the left ventricle and impaired left ventricular performance as in myocardial infarction and heart failure (Krishnamurthy et al 2006; Al‐Rashdan et al 2007). The present study showed that RPC markedly attenuated the reduction in LV(d P /d t ) max / P and rise in LVEDP caused by LAD coronary artery occlusion, suggesting a protective effect of RPC against ischaemia–reperfusion‐induced left ventricular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms

Shahid

Tauseef

Sharma

et al. 2008

Experimental Physiology

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The present study was conducted to examine the role of nitric oxide (NO), mitochondrial ATP-sensitive K + channels (mito K + ATP channels) and reactive oxygen species (ROS) and their interdependence in brief femoral artery ischaemia-induced myocardial preconditioning. To assess myocardial injury, myocardial infarction was induced by occlusion followed by reperfusion of the left anterior descending (LAD) coronary artery in anaesthetized rats and was assessed by triphenyl tetrazolium chloride (TTC) staining. Left ventricular function was assessed by left ventricular end-diastolic pressure (LVEDP) and the maximal rate of rise of left ventricular pressure [LV(dP/dt) max ]. Serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were determined by colorimetric kits. Remote preconditioning (RPC) was induced by 15 min occlusion of femoral arteries followed by 10 min of reperfusion just before LAD coronary artery occlusion. Brief femoral artery ischaemia led to a 61% reduction in myocardial infarct size, 57% reduction in elevated serum LDH and 72% reduction in elevated CK-MB activities, and a significant improvement in LVEDP and LV(dP/dt) max compared with control animals. Pretreatment with 5-hydroxydecanoate (5-HD) or L-NAME or N -acetylcystein (NAC) blocked this protective effect of femoral artery ischaemia. Moreover, infusion of L-arginine or diazoxide before coronary artery occlusion markedly reduced the myocardial infarction and improved the left ventricular function. This effect of L-arginine was found to be abolished by the blockade of mito K + ATP channels with 5-HD and, similarly, the effect of diazoxide was blocked in the presence of a ROS scavenger, NAC. The results suggest that brief femoral artery ischaemia-induced RPC is mediated by a combination of increased NO synthesis, opening of mito K + ATP channels and increased ROS production. Moreover, it appears that NO is working upstream and acts via activation of mito K + ATP channels, which subsequently increases the production of ROS. Ischaemic preconditioning (IPC) is the phenomenon whereby brief episodes of myocardial ischaemia render the ischaemic territory tolerant to subsequent, sustained insult and limit myocardial necrosis (Murry et al. 1986). Remote preconditioning (RPC) is a process in which brief ischaemia in a remote organ or vascular bed may render the heart resistant to subsequent sustained ischaemia (Przyklenk et al. 1993) and has been demonstrated in many models, such as brief occlusion of the mesentric/renal arteries or hindlimb/skeletal muscle ischaemia (Oxman et al. 1997;Pell et al. 1998;Kharbanda et al. 2002;Wang et al. 2002;Weinbrenner et al. 2002;Wolfrum et al. 2002).The benefits observed were a decrease in myocardial infarct size, correction of biochemical markers and endothelial dysfunction, and an anti-arrhythmic effect. To the best of our knowledge, however, the effect of transient femoral artery occlusion-reperfusion in rats on myocardial infarct size and left ventricular function and the post-infarct elevation in serum CK-...

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Section: Discussionmentioning

confidence: 99%

Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms

Shahid

Tauseef

Sharma

et al. 2008

Experimental Physiology

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“…Inflammation and apoptosis have been proposed as potential targets for limiting organ damage following ischemic insult where Ras is thought to play a crucial role in both events. We and others have previously shown that inhibition of Ras-GTPase improves recovery of cardiac function in a perfused rat heart model of global ischemia through a mechanism involving opening of mitochondrial ATP-sensitive potassium channels (Al-Rashdan et al, 2005;Benter et al, 2004;Pando et al, 2009). Interestingly, we found that this beneficial effect is only observed when the Ras inhibitor is administered prior to exposure to ischemia in controls and in models of diabetes and/or hypertension.…”

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confidence: 38%

“…Inhibition of Ras-GTPase signaling by FPTIIIattenuated development of cardiovascular dysfunction in diabetic-hypertensive rats . Recent reports have shown that inhibition of Ras-GTPase with FPTIII improves recovery of cardiac function in a perfused rat heart model of global ischemia through a mechanism involving opening of mitochondrial ATP-sensitive potassium channels (Al-Rashdan et al, 2005;Benter et al, 2004;Pando et al, 2009). Further, Ras appears to amplify NF-kB signaling following activation of IL-1 receptors through IRAK (Zhang et al, 2010).…”

Section: Introductionmentioning

confidence: 96%

Inhibition of Ras-GTPase Farnesylation and the Ubiquitin-Proteasome System or Treatment with Angiotensin-(1–7) Attenuates Spinal Cord Injury-Induced Cardiac Dysfunction

Benter

Abul

Al-Khaledi

et al. 2011

Journal of Neurotrauma

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Cardiovascular diseases are one of the principal causes of death and disability in people with spinal cord injury (SCI). The present study was designed to investigate if acute treatment with FPTIII (an inhibitor of Ras-GTPase farnesylation) or MG132 (an inhibitor of ubiquitin-proteasome pathway [UPS]) or administration of angiotensin-(1-7), also known as Ang-(1-7), (a known inhibitor of cardiac NF-kB) would be cardioprotective. The weight drop technique produced a consistent contusive injury of the spinal cord at the T13 segment. Hearts were isolated from rats either 6 months (SCI-6) or 12 months (SCI-12) after SCI. Hearts were perfused for 30 min and then subjected to 30 min ischemia followed by 30 min reperfusion (I/R). Recovery of cardiac function after I/R was measured as left ventricular developed pressure (P(max)) and coronary flow (CF). Drugs were given during perfusion before hearts were exposed to ischemia and reperfusion. Percent recovery (%R) in P(max) and CF in hearts from control animals were 48±6 and 50±5, respectively, whereas none of the hearts from animals with SCI recovered after 30 min of ischemia. Treatment with FPTIII, MG 132, or Ang-(1-7) before ischemia for 30 min led to significant recovery of heart function following ischemia in SCI-6 but not in SCI-12 animals. Thus we have shown that acute treatments with FPTIII, MG132, or Ang-(1-7) improve cardiac recovery following ischemic insult in animals with SCI and may represent novel therapeutic agents for preventing ischemia-induced cardiac dysfunction in patients with SCI.

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“…Heart perfusion studies were performed as we earlier described. [14][15][16][17] Hearts removed from Group 1 (control) animals were perfused for 30 min. Hearts from Group 2 were perfused for 30 min and then subjected to 40 min ischemia followed by a period of 30 min reperfusion.…”

Section: Animals and Heart Perfusion Studiesmentioning

confidence: 99%

“…Global gene expression profiling may result in insights into the mechanism(s) of cardioprotective effect of IPC to identify intriguing genes and pathways for further study. Information gathered from these studies particularly will be useful when cardio-protective mimetic drugs such as FPTIII [14][15][16] , a specific inhibitor of Ras farnesyltransferase, are used against I-R injury.…”

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confidence: 99%

The effect of cardiac ischemic preconditioning on rat left ventricular gene expression profile

Canatan

2007

Cell Biochemistry & Function

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Ischemic preconditioning (IPC) is a phenomenon where heart is rendered more resistant to subsequent ischemia-reperfusion (I-R)-induced injury by one or more brief episodes of I-R. The mechanisms responsible for cardio-protective effects of IPC are not well characterized. The objective of the study was to characterize gene expression profiles in the left ventricle of male Wistar rat hearts exposed to I-R or IPC followed by I-R. Group 1 included hearts that were only perfused for 30 min. Group 2 included hearts that underwent 30 min perfusion followed by 40 min I and 30 min R. Group 3 comprised 30 min perfused hearts that were subjected to IPC (5 min I + 10 min R + 5 min I + 10 min R) followed by I-R. Total RNAs were isolated from left ventricular tissues. Codelink gene expression system (GE Healthcare) was used for cRNA target preparation, hybridization of microarrays (Rat UniSet 10 K CodeLink bioarrays, GE Healthcare) and detection. Microarrays were scanned with Affymetrix 428 Array scanner. Data analyses were carried out with GeneSifter microarray data analysis software. We determined a total of 140 transcripts (> or =2-fold change) whose expressions were changed (44 up-regulated and 96 down-regulated) accompanying to I-R injury compared to perfused only hearts. Twenty-three transcripts including Ryr3, Crk, Dio1, Npy1r, Ptpra, Cyp51 that were down-regulated by I-R injury, were up-regulated by cardiac IPC. IPC down-regulated the expression of several transcripts including Atf3 (activating transcription factor 3), carboxypeptidase A1 (Cpa1), Slc38a4, Blk which were up-regulated by I-R. In conclusion, evaluation of global gene expression profiling via microarray-based technologies provides a molecular portrait of cardiac IPC of the left ventricular tissue of rat heart.

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Cardioprotection from ischemia‐reperfusion injury due to Ras‐GTPase inhibition is attenuated by glibenclamide in the globally ischemic heart

Cited by 8 publications

References 30 publications

Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms

Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms

Inhibition of Ras-GTPase Farnesylation and the Ubiquitin-Proteasome System or Treatment with Angiotensin-(1–7) Attenuates Spinal Cord Injury-Induced Cardiac Dysfunction

The effect of cardiac ischemic preconditioning on rat left ventricular gene expression profile

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