scholarly journals Enhanced gene expression of Na+/Ca2+exchanger attenuates ischemic and hypoxic contractile dysfunction

2000 ◽  
Vol 279 (6) ◽  
pp. H2846-H2854 ◽  
Author(s):  
Thomas G. Hampton ◽  
Ju-Feng Wang ◽  
Joseph DeAngelis ◽  
Ivo Amende ◽  
Kenneth D. Philipson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Intracellular Calcium ◽  
Systolic Pressure ◽  
Contractile Dysfunction ◽  
Compensatory Mechanism ◽  
Wild Type ◽  
Generating Capacity ◽  
And Function

Enhanced gene expression of the Na+/Ca2+exchanger in failing hearts may be a compensatory mechanism to promote influx and efflux of Ca2+, despite impairment of the sarcoplasmic reticulum (SR). To explore this, we monitored intracellular calcium (Cai 2+) and cardiac function in mouse hearts engineered to overexpress the Na+/Ca2+ exchanger and subjected to ischemia and hypoxia, conditions known to impair SR Cai 2+transport and contractility. Although baseline Cai 2+and function were similar between transgenic and wild-type hearts, significant differences were observed during ischemia and hypoxia. During early ischemia, Cai 2+ was preserved in transgenic hearts but significantly altered in wild-type hearts. Transgenic hearts maintained 40% of pressure-generating capacity during early ischemia, whereas wild-type hearts maintained only 25% ( P < 0.01). During hypoxia, neither peak nor diastolic Cai 2+ decreased in transgenic hearts. In contrast, both peak and diastolic Cai 2+ decreased significantly in wild-type hearts. The decline of Cai 2+ was abbreviated in hypoxic transgenic hearts but prolonged in wild-type hearts. Peak systolic pressure decreased by nearly 10% in hypoxic transgenic hearts and >25% in wild-type hearts ( P < 0.001). These data demonstrate that enhanced gene expression of the Na+/Ca2+ exchanger preserves Cai 2+ homeostasis during ischemia and hypoxia, thereby preserving cardiac function in the acutely failing heart.

Overexpression of Na+/Ca2+ exchanger gene attenuates postinfarction myocardial dysfunction

2002 ◽  
Vol 283 (6) ◽  
pp. H2466-H2471 ◽  
Author(s):  
Jiang-Yong Min ◽  
Matthew F. Sullivan ◽  
Xinhua Yan ◽  
Xin Feng ◽  
Victor Chu ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Contractile Response ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Papillary Muscles ◽  
Wild Type ◽  
Adrenergic Stimulation

We monitored myocardial function in postinfarcted wild-type (WT) and transgenic (TG) mouse hearts with overexpression of the cardiac Na+/Ca2+ exchanger. Five weeks after infarction, cardiac function was better maintained in TG than WT mice [left ventricular (LV) systolic pressure: WT, 41 ± 2; TG, 58 ± 3 mmHg; P < 0.05; maximum rising rate of LV pressure (+dP/d t max): WT, 3,750 ± 346; TG, 5,075 ± 334 mmHg/s; P < 0.05]. The isometric contractile response to β-adrenergic stimulation was greater in papillary muscles from TG than WT mice (WT, 13.2 ± 0.9; TG, 16.3 ± 1.0 mN/mm2 at 10−4 M isoproterenol). The sarcoplasmic reticulum (SR) Ca2+content investigated by rapid cooling contractures in papillary muscles was greater in TG than WT mouse hearts. We conclude that myocardial function is better preserved in TG mice 5 wk after infarction, which results from enhanced SR Ca2+ content via overexpression of the Na+/Ca2+ exchanger.

scholarly journals UDP-Glucose Dehydrogenases: Identification, Expression, and Function Analyses in Upland Cotton (Gossypium hirsutum)

2021 ◽  
Vol 11 ◽  
Author(s):  
Tingting Jia ◽  
Qun Ge ◽  
Shuya Zhang ◽  
Zhen Zhang ◽  
Aiying Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Upland Cotton ◽  
Plant Cell Wall ◽  
Glucuronic Acid ◽  
Glucose Dehydrogenase ◽  
Fiber Development ◽  
Protein Domain ◽  
Cell Wall Synthesis ◽  
Wild Type ◽  
And Function

UDP-glucose dehydrogenase (UGD; EC1.1.1.22) is a NAD+-dependent enzyme that catalyzes the two-fold oxidation of UDP-glucose (UDP-Glc) to produce UDP-glucuronic acid and plays an important role in plant cell wall synthesis. A total of 42 UGD genes from four Gossypium genomes including G. hirsutum, G. arboretum, G. barbadense, and G. raimondii were identified and found that the UGD gene family has conservative evolution patterns in gene structure and protein domain. The growth of fibers can be effectively promoted after adding the UDP-Glc to the medium, and the GhUGD gene expression enhanced. In addition, the transgenic Arabidopsis lines over-expressing GH_D12G1806 had longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. These results indicated that UGD may play important roles in cotton fiber development and has a guiding significance for dissecting fiber development mechanism.

scholarly journals DROSOPHILA MTOR COMPLEX 2 PRESERVES MITOCHONDRIAL AND CARDIAC FUNCTION UNDER HIGH FAT DIET TREATMENT

2021 ◽  
Author(s):  
Kai Chang ◽  
Guillermo A. Requejo Figueroa ◽  
Hua Bai
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Mitochondrial Morphology ◽  
Contractile Dysfunction ◽  
Wild Type ◽  
High Fat ◽  
Mitochondrial Homeostasis ◽  
Mechanistic Target Of Rapamycin ◽  
And Function ◽  
Mtor Complex 1

AbstractHigh fat diet (HFD)-associated lipotoxicity is one of the major causes of cardiovascular diseases. The mechanistic target of rapamycin (mTOR) pathway, especially mTOR complex 1 (mTORC1), has been previously implicated in HFD-induced heart dysfunction. In the present study, we find that unlike mTORC1, mTOR complex 2 (mTORC2) protects hearts from HFD-induced cardiomyopathy and mitochondrial dysfunction in Drosophila. We show that HFD feeding induces contractile dysfunction along with altered mitochondrial morphology and function. Upon HFD feeding, the mitochondria of cardiomyocytes exhibit fragmentation, loss of membrane potential, and calcium overload. Interestingly, HFD feeding also reduces the activity of cardiac mTORC2. In line with this finding, the flies with cardiac-specific knockdown of rictor, the key subunit of mTORC2, show cardiac and mitochondrial dysfunction similar to what is observed in HFD-fed wild-type flies. Conversely, cardiac-specific activation of mTORC2 by overexpressing rictor attenuates HFD-induced mitochondrial and cardiac dysfunction. Thus, our findings suggest that mTORC2 is a cardioprotective factor and regulates mitochondrial homeostasis upon HFD feeding.

Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice

2010 ◽  
Vol 299 (4) ◽  
pp. H1183-H1189 ◽  
Author(s):  
Ava K. Chow ◽  
Edwin E. Daniel ◽  
Richard Schulz
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Wild Type ◽  
Stress Injury ◽  
Caveolin 1 ◽  
Myocardial Oxidative Stress

Matrix metalloproteinases (MMPs) are known to degrade components of the extracellular matrix. More recently, in myocardial oxidative stress injury including ischemia-reperfusion, MMP-2 is activated and degrades troponin I and α-actinin. MMP activity is regulated at several levels. We recently showed that MMP-2 is localized in the caveolae of cardiomyocytes and is negatively regulated by caveolin-1 (Cav-1). The caveolin scaffolding domain of Cav-1 inhibits MMP-2 proteolytic activity in vitro, and Cav-1−/− mouse hearts have increased MMP-2 activity compared with controls. Whether this increase in MMP-2 activity translates to impaired cardiac function is unknown. Hearts isolated from Cav-1−/− mice and their wild-type controls were perfused as isolated working hearts and physiologically challenged with increasing increments of left atrial preload (7–22.5 mmHg). The hearts were then pharmacologically challenged with increasing concentrations of isoproterenol (0.1–100 nM). Functionally, the Cav-1−/− hearts were similar to the controls in heart rate, peak systolic pressure, developed pressure, and rate pressure product. At higher preload pressures, the Cav-1−/− hearts outperformed the control hearts. Coronary flow was significantly higher in Cav-1−/− hearts under all conditions. The highest concentration of isoproternol increased the heart rate of Cav-1−/− hearts more than in controls. Western blot analysis revealed no significant changes in troponin I or α-actinin between Cav-1−/− hearts and their controls. There was a significant loss of MMP-2 from both knockout and control hearts during the perfusion. In summary, despite the loss of Cav-1, Cav-1−/− hearts show similar or better cardiac function compared with wild-type hearts following physiological challenge or β-adrenergic stimulation in vitro, and this appears unrelated to changes in MMP-2.

scholarly journals The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice

2006 ◽  
Vol 37 (2) ◽  
pp. 301-316 ◽  
Author(s):  
Andreas Petri ◽  
Jonas Ahnfelt-Rønne ◽  
Klaus Stensgaard Frederiksen ◽  
David George Edwards ◽  
Dennis Madsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Homeobox Gene ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Gene Expression ◽  
And Function ◽  
Deficient Mice

To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared to controls. Many of them were previously described to be involved in endocrine development and function. Among the genes not previously characterized were Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and the Iroquois-type homeobox gene Irx1, the latter was selected for further investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1 and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon-, but not insulin- or somatostatin-producing cells in mice and chicken. These data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the regulation of α-cell-specific gene expression.

Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma

2003 ◽  
Vol 285 (4) ◽  
pp. H1616-H1625 ◽  
Author(s):  
Jean White ◽  
Deborah L. Carlson ◽  
Marita Thompson ◽  
David L. Maass ◽  
Billy Sanders ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Function ◽  
Total Body Surface Area ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Wild Type ◽  
Burn Trauma ◽  
Cardiac Contractile ◽  
Cardiac Contractile Dysfunction

Whereas controversial, several studies have suggested that nitric oxide (NO) alters cardiac contractility via cGMP, peroxynitrite, or poly(ADP ribose) synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase (iNOS) and NO generation contributes to burn-mediated cardiac contractile dysfunction. Mice homozygous null for the iNOS gene (iNOS knockouts) were obtained from Jackson Laboratory. iNOS knockouts (KO) as well as wild-type mice were given a cutaneous burn over 40% of the total body surface area by the application of brass probes (1 × 2 × 0.3 cm) heated to 100°C to the animals' sides and back for 5 s (iNOS/KO burn and wild-type burn). Additional groups of iNOS KO and wild-type mice served as appropriate sham burn groups (iNOS/KO sham and wild-type sham). Cardiac function was assessed 24 h postburn by perfusing hearts ( n = 7–10 mice/group). Burn trauma in wild-type mice impaired cardiac function as indicated by the lower left ventricular pressure (LVP, 67 ± 2 mmHg) compared with that measured in wild-type shams (94 ± 2 mmHg, P < 0.001), a lower rate of LVP rise (+dP/d tmax, 1,620 ± 94 vs. 2,240 ± 58 mmHg/s, P < 0.001), and a lower rate of LVP fall (–dP/d tmax, 1,200 ± 84 vs. 1,800 ± 42 mmHg/s, P < 0.001). Ventricular function curves confirmed significant contractile dysfunction after burn trauma in wild-type mice. Burn trauma in iNOS KO mice produced fewer cardiac derangements compared with those observed in wild-type burns (LVP: 78 ± 5 mmHg; +dP/d t: 1,889 ± 160 mmHg/s; –dP/d t: 1,480 ± 154 mmHg/s). The use of a pharmacological approach to inhibit iNOS (aminoguanidine, given ip) in additional wild-type shams and burns confirmed the iNOS KO data. Whereas the absence of iNOS attenuated burn-mediated cardiac contractile dysfunction, these experiments did not determine the contribution of cardiac-derived NO versus NO generated by immune cells. However, our data indicate a role for NO in cardiac dysfunction after major trauma.

scholarly journals Identification of Two Subsets of Murine DC1 Dendritic Cells That Differ by Surface Phenotype, Gene Expression, and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
David Hongo ◽  
Pingping Zheng ◽  
Suparna Dutt ◽  
Rahul Pawar ◽  
Everett Meyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Wild Type ◽  
Surface Receptors ◽  
Cytokine Responses ◽  
Th1 Cytokine ◽  
And Function ◽  
Functional Profiles

Classical dendritic cells (cDCs) in mice have been divided into 2 major subsets based on the expression of nuclear transcription factors: a CD8+Irf8+Batf3 dependent (DC1) subset, and a CD8-Irf4+ (DC2) subset. We found that the CD8+DC1 subset can be further divided into CD8+DC1a and CD8+DC1b subsets by differences in surface receptors, gene expression, and function. Whereas all 3 DC subsets can act alone to induce potent Th1 cytokine responses to class I and II MHC restricted peptides derived from ovalbumin (OVA) by OT-I and OT-II transgenic T cells, only the DC1b subset could effectively present glycolipid antigens to natural killer T (NKT) cells. Vaccination with OVA protein pulsed DC1b and DC2 cells were more effective in reducing the growth of the B16-OVA melanoma as compared to pulsed DC1a cells in wild type mice. In conclusion, the Batf3-/- dependent DC1 cells can be further divided into two subsets with different immune functional profiles in vitro and in vivo.

73 INTRAUTERINE GROWTH RESTRICTION AFTER BETWEEN-BREED EMBRYO TRANSFER IS ASSOCIATED WITH STRONG ALTERATIONS IN PLACENTAL STRUCTURE AND FUNCTION IN HORSES

2014 ◽  
Vol 26 (1) ◽  
pp. 150
Author(s):  
P. Peugnet ◽  
S. Valentino ◽  
A. Tarrade ◽  
L. Wimel ◽  
F. Reigner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Embryo Transfer ◽  
Intrauterine Growth Restriction ◽  
Surface Density ◽  
Structure And Function ◽  
Growth Restriction ◽  
Placental Weight ◽  
Compensatory Mechanism ◽  
Intrauterine Growth ◽  
And Function

In equids, placentation is diffuse and the nutrient supply to the fetus is determined by uterine size, which is correlated with maternal size. The size of the mare affects fetal development as shown by embryo transfer (ET) between Ponies and Thoroughbreds. In turn, insulin sensitivity in the newborn foal and subsequent postnatal growth rate are affected. We enhanced or restricted fetal growth through ET using Pony (P), Saddlebred (S), and Draft (D) horses and investigated placental morphology, structure, and function at term. Control pregnancies of P-P (n = 21), S-S (n = 28), and D-D (n = 8) were obtained by AI. Enhanced and restricted pregnancies were obtained by transferring P (P-D, n = 6) and S embryos (S-D, n = 8) into D mares or S embryos into P mares (S-P, n = 6), respectively. Placental weight and surface were recorded at delivery. Samples were collected for stereology and RT-qPCR analysis of expression of genes involved in placental growth, vascularization, and nutrient transport. Housekeeping genes were RPL32, SCAMP3, and B2M. Data were analysed by Kruskal-Wallis followed by Dunn's post hoc test. Placental weight and surface were increased in S-S and in D-D compared with P-P, whereas S-S and D-D were not different. No histological changes were observed among controls, but most genes had their expression decreased in P-P compared with S-S and D-D. The P-D foals had a 57% increased birthweight with heavier and larger placentas than P-P foals. The S-D foals were similar to both S-S and D-D in terms of birthweight and placental weight and surface. No major modifications in placental histology or transcript levels were observed in both enhanced groups. In contrast, S-P foals had a 37% decreased birthweight with lighter and smaller placentas compared with S-S and S-D foals. There was no gross histological difference between S-P and S-S but the microcotyledonary surface density was higher in S-P compared with S-D. Moreover, the expression of IGF2, IGF2R, SLC2A1, and eNOS was decreased in S-P compared with S-S. There was no difference in gene expression between S-P and P-P. In conclusion, intrauterine growth restriction led to marked changes in placental morphology, histology, and gene expression. The increased microcotyledonary surface density suggests a lengthening of villi, which could increase feto-maternal contact surface as a compensatory mechanism for the restricted uterine capacity. Surprisingly, placental adaptation to the restricted intrauterine environment in S-P induced gene profiles resembling that of control P, whereas no difference was observed in enhanced pregnancies.

scholarly journals A New Approach to Improve the Hemodynamic Assessment of Cardiac Function Independent of Respiratory Influence

2021 ◽  
Author(s):  
Leslie Ogilvie ◽  
Brittany A. Edgett ◽  
Simon Gray ◽  
Sally Al-Mufty ◽  
Jason S. Huber ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Function ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Inspiratory Pressure ◽  
Strongly Correlated ◽  
Hemodynamic Assessment ◽  
Respiratory Phase ◽  
Systolic And Diastolic Function ◽  
And Function

Abstract Cardiovascular and respiratory systems are anatomically and functionally linked; inspiration produces negative intrathoracic pressures that act on the heart and alter cardiac function. Inspiratory pressures increase with heart failure and can exceed the magnitude of ventricular pressure during diastole. Accordingly, respiratory pressures may be a confounding factor to assessing cardiac function. While the interaction between respiration and the heart is well characterized, the extent to which systolic and diastolic indices are affected by inspiration is unknown. Our objective was to understand how inspiratory pressure affects the hemodynamic assessment of cardiac function. To do this, we developed custom software to assess and separate indices of systolic and diastolic function into inspiratory, early expiratory, and late expiratory phases of respiration. We then compared cardiac parameters during normal breathing and with various respiratory loads. Variations in inspiratory pressure had a small impact on systolic pressure and function. Conversely, diastolic pressure strongly correlated with negative inspiratory pressure. Cardiac pressures were less affected by respiration during expiration; late expiration was the most stable respiratory phase. In conclusion, inspiration is a large confounding influence on diastolic pressure, but minimally affects systolic pressure. Performing cardiac hemodynamic analysis by accounting for respiratory phase yields more accuracy and analytic confidence to the assessment of diastolic function.

Influence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarction

2004 ◽  
Vol 82 (12) ◽  
pp. 1118-1127 ◽  
Author(s):  
Bin Ren ◽  
Qiming Shao ◽  
Pallab K Ganguly ◽  
Paramjit S Tappia ◽  
Nobuakira Takeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Term Treatment ◽  
Cardiac Performance ◽  
Long Term Treatment

Although it is generally accepted that the efficacy of imidapril, an angiotensin-converting enzyme inhibitor, in congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR) proteins has not been fully understood. In this study, we examined the effects of long-term treatment of imidapril on mortality, cardiac function, and gene expression for SL Na+/K+ ATPase and Na+–Ca2+ exchanger as well as SR Ca2+ pump ATPase, Ca2+ release channel (ryanodine receptor), phospholamban, and calsequestrin in CHF due to myocardial infarction. Heart failure subsequent to myocardial infarction was induced by occluding the left coronary artery in rats, and treatment with imidapril (1 mg·kg–1·day–1) was started orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed hemody nam ically and the heart and lung were examined morphologically. Some hearts were immediately frozen at –70 °C for the isolation of RNA as well as SL and SR membranes. The mortality of imidapril-treated animals due to heart failure was 31% whereas that of the untreated heart failure group was 64%. Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced morphological changes in the heart and lung. The depressed SL Na+/K+ ATPase and increased SL Na+–Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing hearts were partially prevented by imidapril. Although changes in gene expression for SL Na+/K+ ATPase isoforms as well as Na+–Ca2+ exchanger and SR phospholamban were attenuated by treatments with imidapril, no alterations in mRNA levels for SR Ca2+ pump proteins and Ca2+ release channels were seen in the untreated or treated rats with heart failure. These results suggest that the beneficial effects of imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression.Key words: sarcolemmal Na+/K+ ATPase, Na+–Ca2+ exchange, sarcoplasmic reticulum, heart failure, ACE inhibition.

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