Abstract 4364: Gender-Specific Regulation of Ncx in Human Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Constance E Mash ◽  
Wendy E Sweet ◽  
Christine S Moravec
Keyword(s):  
Human Heart ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Ischemia Reperfusion ◽  
Cardiac Transplant ◽  
Heart Cells ◽  
Male Population ◽  
Human Heart Failure ◽  
Male And Female ◽  
Males And Females

We and others have previously reported increased protein levels of the sarcolemmal sodium-calcium exchanger (NCX) in failing (F) vs non-failing (NF) human hearts. In the non-failing cardiomyocyte, NCX transports calcium out of the cell following contraction, in an amount roughly equal to that which enters the cell through L type calcium channels upon depolarization. In the face of decreased sarcoplasmic reticulum calcium ATPase (SERCA) function in the F human heart, up-regulation of NCX is thought to be a compensatory change, helping to prevent calcium overload. It has also been demonstrated that NCX may work in reverse mode in F heart cells, providing for increased calcium influx during the action potential plateau. Recent studies have suggested that over-expression of NCX has different functional consequences in male and female animal hearts during metabolic inhibition as well as ischemia/reperfusion injury, yet studies demonstrating up-regulation of NCX in F human hearts have largely pooled male and female hearts. We have measured NCX and SERCA in a population of male and female F and NF human hearts. Nine patients were studied per group. F hearts were explanted from cardiac transplant recipients with diagnosis of dilated cardiomyopathy and NF hearts from unmatched organ donors. Immunoblotting was used to quantify NCX and SERCA, normalized to actin. NCX was increased in both male and female F hearts as compared to NF hearts, but the increase was proportionately greater in the male population (Normalized values: Male F 3.30 vs NF 1.0; Female F 2.60 vs NF 1.0). Comparison of NF hearts from males and females, however, demonstrated that levels of NCX protein are consistently higher in female than male hearts (Female NF 2.18 vs Male 1.0). SERCA protein was decreased in both male and female F hearts to equal degrees as compared to both groups of NF hearts (Male F 0.65 vs NF 1.0; Female F 0.65 vs NF 1.0), with no difference in NF levels between males and females (female NF 1.1 vs Male 1.0). These data suggest that NCX is regulated differently in male and female F human hearts, which may play a role in the ability of the heart to preserve adequate calcium cycling during cardiac dysfunction.

scholarly journals Noninvasive Imaging of Activated Complement in Ischemia-Reperfusion Injury Post-Cardiac Transplant

2015 ◽  
Vol 15 (9) ◽  
pp. 2483-2490 ◽  
Author(s):  
E. Sharif-Paghaleh ◽  
M. L. Yap ◽  
L. L. Meader ◽  
K. Chuamsaamarkkee ◽  
F. Kampmeier ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Noninvasive Imaging ◽  
Cardiac Transplant

Abstract 300: Topical Application of IcyHot Reduces Myocardial Infarct Size in Rodents by a TRPA1-dependent Mechanism

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Yun Wu ◽  
Yao Lu ◽  
Eric R Gross
Keyword(s):  
Infarct Size ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Sprague Dawley ◽  
Area At Risk ◽  
Reactive Aldehydes

Toxic reactive aldehydes are formed during ischemia-reperfusion. The ion channel transient receptor potential ankryin 1 (TRPA1) is irreversibly modified by reactive aldehydes which can cause calcium influx and cell death. Here we tested whether topically applied creams containing a reversible TRPA1 agonist could reduce myocardial infarct size. Male Sprague-Dawley rats 8-10 weeks age were subjected to an in vivo myocardial ischemia-reperfusion model of 30 minutes of left anterior descending (LAD) coronary artery ischemia followed by 2 hours reperfusion. Prior to ischemia, rats were untreated or had 1g of cream applied to the abdomen. The creams tested were IcyHot, Bengay, Tiger Balm, or preparation H (Fig. 1A). Hearts were negatively stained for the area at risk and the infarct size was determined by using TTC staining (Fig. 1B). A subset of rodents prior to receiving IcyHot also received an intravenous bolus of the TRPA1 antagonist TCS-5861528 (1mg/kg) or AP-18 (1mg/kg). Interestingly, both IcyHot and Bengay reduced myocardial infarct size compared to untreated rodents (Fig. 1C and 1D IcyHot: 41±3%*, Bengay: 50±2%* versus control 62±1%, n=6/group, *P<0.001). Both preparation H and Tiger Balm failed to reduce myocardial infarct size (Tiger Balm: 63±2%, preparation H 59±2%). Giving a TRPA1 antagonist prior to IcyHot also blocked the reduction in infarct size. Our additional data also indicates the methyl salicylate (mint) in IcyHot and Bengay is the agent that limits myocardial infarct size. Since IcyHot and Bengay are safely used by humans, targeting TRPA1 by using products such as these could be quickly translatable and widely used to reduce ischemia-reperfusion injury.

Abstract 11710: Poloxamer 188 Protects Coronary Artery Endothelial Cells After Extended Hypoxia and Reoxygenation in an in vitro Model of Simulated Ischemia/Reperfusion Injury

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
zhu li ◽  
Matthew J Hampton ◽  
Matthew B Barajas ◽  
Matthias L Riess
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Membrane Function ◽  
Ldh Release

Reperfusion restores blood flow after myocardial ischemia but can cause additional cellular injury by the sudden reintroduction of oxygen and nutrients. There is still no effective remedy for myocardial ischemia/reperfusion (IR) injury. Our previous study using cardiomyocytes (CMs) found that, after 3 hrs hypoxia followed by 2 hrs reoxygenation, viability decreased, and release of lactate dehydrogenase (LDH), calcium influx, membrane leakage (insertion of fluorescent probe FM1-43) significantly increased, indicating that cell membrane function was negatively affected. This was attenuated by the triblock copolymer Poloxamer (P)188. Here, we first hypothesized that endothelial cells are also susceptible to simulated IR injury, albeit requiring longer hypoxia times. We further hypothesized that P188 can also attenuate simulated IR injury in endothelial cells when given upon reoxygenation. Mouse coronary artery endothelial cells (MCAECs) were exposed to different durations of hypoxia (2, 3, 12 and 24 hrs) in serum- and glucose-free media +/- reoxygenation for 2 hrs in regular media. P188 was administered upon reoxygenation at 0, 100, 300 or 1,000 μM in experiments of 24 hrs hypoxia / 2 hrs reoxygenation. LDH release was measured and compared to appropriately timed normoxic control experiments. Reoxygenation and hypoxia times significantly longer than 3 hrs were required to elicit sufficient injury (panel A). When P188 was given upon reoxygenation after 24 hrs hypoxia, it dose-dependently attenuated LDH release (panel B). These findings contrast to the higher susceptibility of CMs to IR injury that only allowed shorter hypoxia durations. They also confirm a protective effect of P188 on the endothelium, not just on CMs. These findings have important implications for co-culture models with MCAECs and CMs to elucidate the interplay of both cell types on each other when studying mechanisms of cardioprotective strategies and compounds like P188.

Developmental and sex differences in cardiac tolerance to ischemia–reperfusion injury: the role of mitochondria

2019 ◽  
Vol 97 (9) ◽  
pp. 808-814 ◽  
Author(s):  
B. Ostadal ◽  
Z. Drahota ◽  
J. Houstek ◽  
M. Milerova ◽  
I. Ostadalova ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Regulatory Protein ◽  
Lower Sensitivity ◽  
Cyclophilin D ◽  
Male And Female ◽  
Postnatal Maturation ◽  
High Calcium ◽  
Age And Sex

Age and sex play an essential role in the cardiac tolerance to ischemia–reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia–reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium.

Gender Differences in Cardiac Ischemic Injury and Protection—Experimental Aspects

2009 ◽  
Vol 234 (9) ◽  
pp. 1011-1019 ◽  
Author(s):  
Bohuslav Ostadal ◽  
Ivan Netuka ◽  
Jiri Maly ◽  
Josef Besik ◽  
Ivana Ostadalova
Keyword(s):  
Gender Differences ◽  
Hormone Receptors ◽  
Ischemia Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Steroid Hormone Receptors ◽  
Natural Resistance ◽  
Cellular Mechanisms ◽  
Male And Female

This review summarizes some available information on gender differences of myocardial injury with particular attention to experimental approach. It has been observed that significant gender differences exist already in normal heart. They involve among others cardiac growth, contractile function, calcium metabolism and function of mitochondria. Differences, characteristic of the normal myocardium, generate the logical presumption of the different reaction of the male and female heart to various pathogenic factors. Most of the experimental studies confirm the clinical observations: increased resistance of the female heart to ischemia/reperfusion injury was shown in dogs, rats, mice and rabbits. Furthermore, gender differences in the ischemic tolerance of the adult myocardium can be influenced by interventions (e.g. hypoxia) imposed during the early phases of ontogenetic development. The already high tolerance of the adult female heart can be increased by adaptation to chronic hypoxia and ischemic preconditioning. It seems that the protective effect depends on age: it was absent in young, highly tolerant heart but it appeared with the decrease of natural resistance during aging. Both experimental and clinical studies have indicated that female gender influences favorably also the remodeling and the adaptive response to myocardial infarction. It follows from the data available that male and female heart differs significantly in many parameters under both physiological and pathological conditions. Detailed molecular and cellular mechanisms of these differences are still unknown; they involve genomic and non-genomic effects of sex steroid hormones, particularly the most frequently studied estrogens. The cardiovascular system is, however, influenced not only by estrogens but also by other sex hormones, e.g. androgens. Moreover, steroid hormone receptors do not act alone but interact with a broad array of co-regulatory proteins to alter transcription. The differences are so important that they deserve serious consideration in clinical practice in search for proper diagnostic and therapeutic procedures.

scholarly journals Male and Female Rats Have Different Physiological Response to High-Fat High-Sucrose Diet but Similar Myocardial Sensitivity to Ischemia-Reperfusion Injury

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2914
Author(s):  
Natacha Fourny ◽  
Carole Lan ◽  
Monique Bernard ◽  
Martine Desrois
Keyword(s):  
Reperfusion Injury ◽  
Glucose Intolerance ◽  
Physiological Response ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Fat ◽  
Male And Female ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

Prediabetes is a strong predictor of type 2 diabetes and its associated cardiovascular complications, but few studies explore sexual dimorphism in this context. Here, we aim to determine whether sex influences physiological response to high-fat high-sucrose diet (HFS) and myocardial tolerance to ischemia-reperfusion injury. Male and female Wistar rats were subjected to standard (CTRL) or HFS diet for 5 months. Then, ex-vivo experiments on isolated perfused heart model were performed to evaluate tolerance to ischemia-reperfusion injury. HFS diet induced fasting hyperglycemia and increased body fat percent to a similar level in both sexes. However, glucose intolerance was more pronounced in female HFS. Cholesterol was increased only in female while male displayed higher level of plasmatic leptin. We observed increased heart weight to tibia length ratio only in males, but we showed a similar decrease in tolerance to ischemia-reperfusion injury in female and male HFS compared with respective controls, characterized by impaired cardiac function, energy metabolism and coronary flow during reperfusion. In conclusion, as soon as glucose intolerance and hyperglycemia develop, we observe higher sensitivity of hearts to ischemia-reperfusion injury without difference between males and females.

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