Pyridine nucleotides and the reduction of GSSG in hypoxic heart tissue exposed to diamide

1993 ◽  
Vol 15 (5) ◽  
pp. 520 ◽  
Author(s):  
James P. Kehrer ◽  
Loren G. Lund ◽  
Thomas Paraidathathu
Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kalyan C Chapalamadugu ◽  
Jared Tur ◽  
Javier Cuevas ◽  
Chris Katnik ◽  
Srinivas M Tipparaju

Background: Voltage-gated potassium channel (Kv) β2 subunits (Kvβ2) belong to the aldoketo-reductase superfamily and associate with the Kv channel modulating its function. Also, Kvβ2 binds pyridine nucleotides (NAD[P] + /NAD[P]H) with high affinity altering Kv channel gating. However, the physiological relevance of Kvβ2 in cardiac health and disease is unknown. Hypothesis: We tested the hypothesis that Kvβ2 is essential to both basal and pyridine nucleotide mediated regulation of cardiac repolarization. Methods and Results: Kvβ2 knockout (KO) and wild type (Wt) mice were utilized for this study. ECG analysis showed prolonged QTc interval (74.7± 3.7 vs. 65.6 ± 3, n=3 , p<0.05 ) in KO mice when compared to Wt. Monophasic action potential (MAP) data also showed prolonged duration (ms) at 50% repolarization level in KO mouse hearts vs. Wt (MAPD50; 13.2 ± 0.3 vs. 9.7 ± 0.6, n=5-6 , p<0.05 ). To test the obligatory role of Kvβ2 in pyridine nucleotide modulation of cardiac repolarization, we exposed ex vivo perfused hearts or isolated cardiomyocytes to higher lactate levels. These data revealed that acute lactate exposure leads to significant but similar raise in NADH concentration [NADH] i in both KO and Wt heart tissue. However, marked repolarization deficits appeared only in Wt group when tested utilizing ex vivo perfused hearts (MAPD50 - Wt:11.5 ± 0.7 vs. 8.3 ± 0.5, p<0.05 ; KO:12.6 ± 0.7 vs. 12± 0.5, p=0.5 , ms) or isolated myocytes (ΔAPD50 – Wt: 4.7±1.6 ms, p<0.05 ; KO:1.5 ± 0.7 ms, p=0.1 ). Perfusion with high pyruvate levels returned both [NADH] i and MAPD50 to basal levels in Wt mouse hearts. Similarly, we observed that a 14 day isoproterenol treatment also leads to significant increase in cardiac [NADH] i , but only the Wt mouse hearts showed significant repolarization deficits; ex-MAPD50 (5.5 ± 1.6, p< 0.01 ), when compared to no changes in KO (1.9 ± 0.9, p< 0.1) . Conclusions: Our results suggest that Kvβ2 regulates cardiac repolarization. Further, the differential repolarization changes despite similar increases in cardiac [NADH] i indicates an obligatory role of Kvβ2 in the pyridine nucleotide modulation of cardiac repolarization.


2013 ◽  
Vol 61 (S 01) ◽  
Author(s):  
L Conradi ◽  
S Schmidt ◽  
L Peters ◽  
A Eder ◽  
A Hansen ◽  
...  

The strategy of heart tissue engineering is simple enough: first remove all the cells from a organ then take the protein scaffold left behind and repopulate it with stem cells immunologically matched to the patient in need. While various suc- cessful methods for decellularization have been developed, and the feasibility of using decellularized whole hearts and extracellular matrix to support cells has been demonstrated, the reality of creating whole hearts for transplantation and of clinical application of decellularized extracellular matrix-based scaffolds will require much more research. For example, further investigations into how lineage-restricted progenitors repopulate the decellularized heart and differentiate in a site-specific manner into different populations of the native heart would be essential. The scaffold heart does not have to be human. Pig hearts carries all the essential components of the extracellular matrix. Through trial and error, scaling up the concentration, timing and pressure of the detergents, researchers have refined the decellularization process on hundreds of hearts and other organs, but this is only the first step. Further, the framework must be populated with human cells. Most researchers in the field use a mixture of two or more cell types, such as endothelial precursor cells to line blood vessels and muscle progenitors to seed the walls of the chambers. The final challenge is one of the hardest: vasculariza- tion, placing a engineered heart into a living animal, integration with the recipient tissue, and keeping it beating for a long time. Much remains to be done before a bioartificial heart is available for transplantation in humans.


2021 ◽  
Vol 22 (9) ◽  
pp. 5006
Author(s):  
Jelica Grujić-Milanović ◽  
Vesna Jaćević ◽  
Zoran Miloradović ◽  
Djurdjica Jovović ◽  
Ivica Milosavljević ◽  
...  

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.


Aquaculture ◽  
2021 ◽  
Vol 541 ◽  
pp. 736847
Author(s):  
Sildiane Martins Cantanhêde ◽  
Lílian Lund Amado ◽  
Brenda Maria P. Alho da Costa ◽  
Luis André L. Barbas ◽  
Marcelo Ferreira Torres ◽  
...  

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Martha Alicia Ballinas-Verdugo ◽  
Rogelio Frank Jiménez-Ortega ◽  
Eduardo Martínez-Martínez ◽  
Nancy Rivas ◽  
Erick Abraham Contreras-López ◽  
...  

Abstract Background Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. Results Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. Conclusions The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.


1950 ◽  
Vol 185 (2) ◽  
pp. 741-747 ◽  
Author(s):  
Philip. Feigelson ◽  
J.N. Williams ◽  
C.A. Elvehjem

2021 ◽  
pp. 096032712110028
Author(s):  
F Kar ◽  
İ Söğüt ◽  
C Hacıoğlu ◽  
Y Göncü ◽  
H Şenturk ◽  
...  

Background: Hexagonal boron nitride nanoparticles (hBN NPs) are encouraging nanomaterials with unique chemical properties in medicine and biomedical fields. Until now, the optimal hBN NP’s dosage and biochemical mechanism that can be used for in vivo systems has not been fully revealed. The main aim of this article is to reveal characteristics, serum and tissue interactions and any acute cytotoxic effect of different dose of hBN NPs for the first time. Methods: hBN NPs at concentrations varying between 50–3200 µg/kg was administered by intravenous injection to Wistar albino rats (n = 80) divided into seven dosage and control groups. Blood and tissue samples were taken after 24 hours. Results: Our findings suggested that higher doses hBN NPs caused oxidative stress on the serum of rats dose-dependently. However, hBN NPs did not affect thiol/disulfide homeostasis on kidney, liver, spleen, pancreas and heart tissue of rats. Furthermore, hBN NPs increased serum disulfide formation by disrupting the thiol/disulfide balance in rats. Also, LOOH and MPO levels increased at high doses, while CAT levels decreased statistically. Conclusion: The results revealed that hBN NPs induce oxidative stress in a dose-dependent manner by modulating thiol/disulfide homeostasis in rats at higher concentrations


Micromachines ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 386
Author(s):  
Ana Santos ◽  
Yongjun Jang ◽  
Inwoo Son ◽  
Jongseong Kim ◽  
Yongdoo Park

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.


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