The present study has been designed to investigate the possible role of protein kinase C-delta (PKC-delta) in hyperhomocysteinemia-induced attenuation of cardioprotective potential of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and ...

Aldehydes are common reactive constituents of food, water and air. Several food aldehydes are potentially carcinogenic and toxic; however, the direct effects of dietary aldehydes on cardiac ischemia-reperfusion (IR) injury are unknown. We tested the hypothesis that dietary consumption of aldehydes modulates myocardial IR injury and preconditioning. Mice were gavage-fed the ...

Rationale: Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD(+)-dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of ...

Mitochondrial permeability transition (MPT) pores have recently been implicated as a potential mediator of myocardial ischemic injury. Nitric oxide (NO) donors induce a powerful late phase of cardioprotection against ischemia-reperfusion injury; however, the cellular mechanisms involved are poorly understood. The role of MPT pores as a target of ...

... treatment with G2-phase checkpoint abrogators may sensitize cancer cells ... development of drugs that abrogate the G2-phase checkpoint for potential ... ...

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new ...

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new ...

Interleukin (IL)-6 family cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, play important roles in the maintenance of cardiac homeostasis. IL-11, a member of IL-6 family cytokines, is expressed in cardiac myocytes, though it remains to be elucidated how IL-11 functions in the hearts. In the present study, first, we showed that IL-11 administration reduced ...

BackgroundAlthough remote ischemic stimuli have been shown to elicit cardioprotection against ischemia/reperfusion injury, there is little known about the effects of nonischemic stimuli. We previously described a remote cardioprotective effect of nonischemic surgical trauma (abdominal incision) called remote preconditioning of trauma (RPCT). In the present ...

The attractiveness of immunomodulator therapy for infectious disease in burns is that it abrogates the potential development of antibiotic-resistant strains of bacteria, and in addition, the spectrum of activity of an immuno-therapeutant may be considerab...

PKC? is central to cardioprotection. Sub-proteome analysis demonstrated co-localization of activated cardiac PKC? (aPKC?) with metabolic, mitochondrial, and cardioprotective modulators like hypoxia-inducible factor 1? (HIF-1?). aPKC? relocates to the mitochondrion, inactivating glycogen synthase kinase 3? (GSK3?) to modulate glycogen metabolism, ...

PKC? is central to cardioprotection. Sub-proteome analysis demonstrated co-localization of activated cardiac PKC? (aPKC?) with metabolic, mitochondrial, and cardioprotective modulators like hypoxia inducible factor 1? (HIF-1?). aPKC? relocates to the mitochondrion, inactivating glycogen synthase kinase 3? (GSK3?) to modulate glycogen metabolism, ...

Autophagy is a critical cellular housekeeping process that is essential for removal of damaged or unwanted organelles and protein aggregates. Under conditions of starvation, it is also a mechanism to break down proteins to generate amino acids for synthesis of new and more urgently needed proteins. In the heart, autophagy is upregulated by starvation, reactive oxygen species, hypoxia, exercise, ...

Nitric oxide (NO) has been implicated as a cardioprotective agent during ischemia/reperfusion (I/R), but the mechanism of protection is unknown. Oxidant stress contributes to cell death in I/R, so we tested whether NO protects by attenuating oxidant stress. Cardiomyocytes and murine embryonic fibroblasts were administered NO (10-1200 nM) during simulated ischemia, and cell ...

Important sex differences in cardiovascular disease outcomes exist, including conditions of hypertrophic cardiomyopathy and cardiac ischemia. Studies of sex differences in the extent to which load-independent (primary) hypertrophy modulates the response to ischemia-reperfusion (I/R) damage have not been characterized. We have previously described a model of primary genetic cardiac hypertrophy, the ...

Although the adenosine A(3) receptor agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) has been reported to be cardioprotective at reperfusion, little is known about the mechanisms underlying the protection. We hypothesized that IB-MECA may protect the heart at reperfusion by preventing the opening of mitochondrial permeability transition pore (mPTP) ...

Medicinal plants have been widely recognized as a renewable resource for the discovery of novel leads and drug. In this study, an approach for screening and identification compounds with cardioprotective activity from medicinal plant extracts by cellular-fluorescence imaging technique was developed. It is a cell-based assay for measuring mitochondrial membrane ...

Salusin-alpha and salusin-beta are newly identified bioactive peptides with hemodynamic and mitogenic activities. Recent studies have shown that salusins improve calcium uptake and protein synthesis in neonatal rat cardiomyocytes, suggesting that salusins may be regulatory factors for myocardial growth and hypertrophy. In this study, we investigated whether salusins improve the survival of ...

Mitochondria are an important source of reactive oxygen species (ROS), implicated in ischemia/reperfusion injury. When isolated from ischemic myocardium, mitochondria demonstrate increased ROS production as a result of damage to electron transport complexes. To investigate the mechanisms, we studied effects of hypoxia/reoxygenation on ROS production by isolated energized heart mitochondria. ROS ...

Mitochondria are an important source of reactive oxygen species (ROS) implicated in ischemia/reperfusion injury. When isolated from ischemic myocardium, mitochondria demonstrate increased ROS production as a result of damage to electron transport complexes. To investigate the mechanisms, we studied effects of hypoxia/reoxygenation on ROS production by isolated energized heart mitochondria. ROS ...

Hsp20 is chaperone protein that is highly and constitutively expressed in the brain, cardiac tissue and many other organs. Recently, it is well established that Hsp20 can enhance cardiac function and render cardioprotection. However, the potential benefits of Hsp20 and its phosphorylation form action on ischemic stroke and its underlying mechanism(s) are ...

We have recently shown that the inhibition of histone deacetylases (HDAC) protects the heart against ischemia and reperfusion (I/R) injury. The mechanism by which HDAC inhibition induces cardioprotection remains unknown. We sought to investigate whether the genetic disruption of gp-91, a subunit of NADPH-oxidase, would mitigate cardioprotection of HDAC ...

Previous work described ATP-sensitive K(+) channel (K(ATP)) openers (e.g., BMS-180448), which retain the cardioprotective activity of agents such as cromakalim while being significantly less potent as vasodilators. In this study, we describe the pharmacologic profile of BMS-191095, which is devoid of peripheral vasodilating activity while retaining glyburide-reversible ...

Mitochondria play a central role in heart energy metabolism and Ca(2+) homeostasis and are involved in the pathogenesis of many forms of heart disease. The body of knowledge on mitochondrial pathophysiology in living cells and organs is increasing, and so is the interest in mitochondria as potential targets for cardioprotection. This critical review will ...

The peptides in the venoms of predatory marine snails belonging to the genus Conus ('cone snails') have well-established therapeutic applications for the treatment of pain and epilepsy. This review discusses the neuroprotective and cardioprotective potential of four families of Conus peptides (conopeptides), including omega-conotoxins that target ...

The peptides in the venoms of predatory marine snails belonging to the genus Conus (�cone snails�) have well-established therapeutic applications for the treatment of pain and epilepsy. This review discusses the neuroprotective and cardioprotective potential of four families of Conus peptides (conopeptides), including ?-conotoxins that target ...

with cardioprotective interventions while the second attempts to replace the infarcted myocardium using progenitor cells and speculate on their future potential. The next three speakers will probe the role of autophagy in the ischemic heart. Autophagy is a mechanism whereby proteins and even whole organelles are encapsulated

1. Acute myocardial ischaemia and reperfusion trigger cardioprotective mechanisms that tend to limit myocardial injury. These cardioprotective mechanisms remain for a large part unknown, but can be potentiated by performing ischaemic preconditioning or by administering drugs such as angiotensin-I-converting enzyme (kininase II) ...

The peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a regulator of anti-inflammatory genes. One of its agonists, rosiglitazone-widely used in the treatment of type 2 diabetes mellitus-has recently been reported to increase the risk for myocardial infarction. In contrast, various studies provide evidence for a rosiglitazone-induced cardioprotection in different ...

Context: Antimitogenic effects of estradiol on vascular smooth muscle cells (VSMCs) may be cardioprotective, and these effects are mediated by estrogen receptor-?-dependent and -independent mechanisms, with the latter involving the conversion of estradiol to 2-hydroxyestradiol/2-methoxyestradiol by CYP450. Because resveratrol inhibits CYP450 and is an estrogen-receptor-? ...

Cyclosporine A is a well-known immunosuppressor agent universally used in allotransplantation. However, it has been demonstrated that this drug produces side-effects in several organs, particularly in the kidney and in the heart. Nigella sativa oil has long been used in folk medicine for a wide range of illnesses. One of the potential properties of N. sativa oil is the ability ...

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have shown cardioprotective and renoprotective properties. These agents are recommended as first-line therapy for the treatment of hypertension and the reduction of cardiovascular risk. Early studies pointed to the cardioprotective and renoprotective effects of ARBs ...

Physical inactivity is increasingly recognized as modifiable behavioral risk factor for cardiovascular diseases. A partial list of proposed mechanisms for exercise-induced cardioprotection include induction of heat shock proteins, increase in cardiac antioxidant capacity, expression of endoplasmic reticulum stress proteins, anatomical and physiological changes in the coronary ...

Objective:The cardioprotective potential of human recombinant erythropoietin (alpha) (Epo) against ischemia-reperfusion-induced injury is well known. But, the underlying mechanisms are not well elucidated. The aim of this study was to characterize the mechanism involved in the cardioprotective effect of Epo-induced preconditioning in ...

BackgroundNitric oxide (NO) is cardioprotective and a mediator of ischemic preconditioning (IP). Endothelial nitric oxide synthase (eNOS) is protective against myocardial ischemic injury and a component of IP but the role and location of neuronal nitric oxide synthase (nNOS) remains unclear. Therefore, the aims of these studies were to: (i) investigate the role of nNOS in ...

Pharmacological studies have shown that signal transducers and activators of transcription (STATs) are necessary for the delayed cardioprotection of ischemic preconditioning (PC). However, pharmacologic STAT inhibitors are not specific; furthermore, the individual role of STAT3 in late PC remains unknown. The objectives of the study were (i) to create an inducible, ...

Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with 5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent ...

Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5�min regional ischemia alternating with 5�min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent ...

Increasing evidence indicates that high levels of serum erythropoietin (Epo) can lessen ischemia-reperfusion injury in the heart and multiple cardiac cell types have been suggested to play a role in this Epo effect. To clarify the mechanisms underlying this cardioprotection, we explored Epo treatment of coronary artery endothelial cells and Epo ...

The diabetic heart is known to be susceptible to ischemia/reperfusion (I/R) injury by increased oxidative stress. Although oxidative stress upregulates inducible nitric oxide (iNOS), the role of iNOS in I/R injury in the diabetic heart has been poorly understood. Because iNOS-derived nitric oxide (NO) plays a crucial role in cardioprotection against I/R injury, we hypothesized ...

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K_ATP) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG ...

The "metabolic cocktail" comprising glucose-insulin-potassium administrated at reperfusion reduces infarct size in the in vivo rat heart. We propose that insulin is the major component mediating this protection and acts via Akt prosurvival signaling. This hypothesis was studied in isolated perfused rat hearts (measuring infarct size to area of risk [%]) subjected to 35 minutes regional myocardial ...

The reduced efficacy of cardioprotective interventions in the aged female heart, including estrogen replacement, highlights the need for alternative therapeutics to reduce myocardial ischemia/reperfusion (I/R) injury in post-menopausal women. Here, we sought to determine the efficacy of protein kinase C? (PKC?)- mediated cardioprotection in the aged, ...

Intermittent hypobaric hypoxia (IHH) protects hearts against ischemia/reperfusion (I/R) injury, but the underlying mechanisms are far from clear. Reactive oxygen species (ROS) are paradoxically regarded as a major cause of myocardial I/R injury and a trigger of cardioprotection. In the present study, we investigated whether the ROS generated during early reperfusion contribute ...

Preventive treatment with cannabinoid agonists has been reported to reduce the infarct size in a mouse model of myocardial ischemia/reperfusion. Here we investigated the possible cardioprotective effect of selective CB(2) cannabinoid receptor activation during ischemia. We performed left coronary artery ligature in C57Bl/6 mice for 30 min, followed by 24 h of reperfusion. Five ...

The mitochondrial isoform of aldehyde dehydrogenase (ALDH2) plays a key role in the metabolism of acetaldehyde and other toxic aldehydes. A recent seminal finding has indicated a potential role of ALDH2 activation in the cardioprotection against ischemic injury. Data from our group unveiled a myocardial protective effect of ALDH2 against ...

Doctors have been promoting alcohol as a health tonic for a very long time. The last 30 years has seen the accumulation of a considerable medical literature investigating the potential role of alcohol use as a protection against coronary heart disease. When viewed through the lens of two major early reviews in the mid-1980s, Sir Richard Doll's contributions of the mid-1990s, ...

S-nitrosation (SNO) of mitochondrial protein cysteines can be cardioprotective. Several targets have been implicated, yet the scope and identification of specific residues has not been fully assessed. To address this, a comprehensive assessment of mitochondrial SNO-modifiable cysteines was performed to determine nitric oxide (NO) susceptible pathways and identify novel ...