Increased DNA Damage and Decreased H-MYH Protein Expression in Human Myocardium with End-Stage Congestive Heart Failure

2001 ◽  
Vol 7 (S2) ◽  
pp. 72-73
Author(s):  
R. Lin ◽  
Y. Dong ◽  
J.V. Conte ◽  
A-L Lu-Chang ◽  
C. Wei
Keyword(s):  
Heart Failure ◽  
Dna Damage ◽  
Congestive Heart Failure ◽  
Oxidative Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Dna Lesions ◽  
Human Myocardium ◽  
End Stage

The reactive oxygen species (ROS) such as superoxide radical (O2), hydrogen peroxide (H2O2), and hydroxyl radical (OH), plays a critical role in the pathogenesis of hypertension, atherosclerosis, ischemia-reperfusion injury, stroke, myocardial infarction, and congestive heart failure. A recent study demonstrated that the frequency of mutation in a reporter gene increased in cortical DNA after forebrain ischemia-reperfusion. Eight DNA lesions that are characteristic of DNA damage mediated by free radicals were detected. Among the different oxidative-damage DNA products, 8-oXo-7,8-dihydrodeoxyguanine (8-oxoG) is the most stable and deleterious adduct. Recent studies demonstrated that human MutY homologue (hMYH) protein plays important role in repairing oxidative damage. to date, there is no information regarding the role of hMYH expression in human myocardium with congestive heart failure (CHF). Therefore, the current study designed to investigate the levels of hMYH expression and 8-oxoG in myocardium in the absence or presence of end-stage congestive heart failure. The hypothesis of this study is that increasing DNA damage such as 8-oxoG generation is associated with a reduction of hMYH expression in human myocardium with congestive heart failure.

Increasing Transforming Growth Factor Beta-1 and its Receptor Expression in Human Myocardium with End-Stage Congestive Heart Failure.

2000 ◽  
Vol 6 (S2) ◽  
pp. 612-613
Author(s):  
S. Ren ◽  
C. Wei
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Normal Subjects ◽  
Human Myocardium ◽  
Receptor Expression ◽  
Growth Factor Beta ◽  
End Stage

Transforming growth factor-beta (TGF-β) is a growth-regulating peptide that has been shown to enhance collagen production both in vivo and in vitro. The previous studies demonstrated that TGF-β 1 is present in the normal animal myocardium. However, the expression and localization of TGF-β 1 and TGF-P receptor in human myocardium remain unclear. Therefore, the present study was designed to determine the TGF-β 1 and its receptor in human myocardium in normal subjects and in patients with end-stage congestive heart failure (CHF).Human ventricular tissues were obtained from five normal subjects and five patients with end-stage CHF during cardiac transplantation. TGF-β 1 and TGF-beta type I receptor (TGF-βRI) were determined by immunohistochemical staining (IHCS). The results of IHCS was evaluated by staining density scores (0, no staining; 1, minimal staining; 2, mild staining; 3, moderate staining; and 4, strong staining). The positive staining area (+%) in entire section was also determined.

Decrease Tyrosine Phosphorylation of Stat3 in Human Myocardium with End-Stage Congestive Heart Failure

2000 ◽  
Vol 6 (S2) ◽  
pp. 596-597
Author(s):  
C. Wei ◽  
J. S. McLaughlin
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Protein Expression ◽  
Cardiac Tissue ◽  
Normal Subjects ◽  
Human Myocardium ◽  
Stat3 Phosphorylation ◽  
Normal Human ◽  
Human Cardiac Tissue ◽  
End Stage

Recent study demonstrated that decrease signal transducer and activator of transcription-3 (STAT3) phosphorylation and increase apoptosis might be a critical point in the transition between compensatory cardiac hypertrophy and heart failure. To date, the protein expression of STAT3 in normal and failing human heart remains unclear. Therefore, the current study was designed to investigate the protein expression of STAT3 in human myocardium with end-stage congestive heart failure (CHF) and compared with that in normal human cardiac tissue.Human cardiac atrial tissue was obtained from normal subjects (n=5) and end-stage CHF patients (n=5) during cardiac transplantation. To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. An average of 1000 nuclei was analyzed for TUNEL study. STAT3 protein expression and phosphorylation of STAT3 were determined by immunohistochemical staining (IHCS) with total STAT3 and phospho-specific STAT3 antibodies.

Spermidine/spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest

2007 ◽  
Vol 292 (3) ◽  
pp. C1204-C1215 ◽  
Author(s):  
Kamyar Zahedi ◽  
John J. Bissler ◽  
Zhaohui Wang ◽  
Anuradha Josyula ◽  
Lu Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Dna Repair ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dna Lesions ◽  
Cell Cycle Checkpoint ◽  
Cycle Checkpoint

Expression of spermidine/spermine N1-acetyltransferase (SSAT) increases in kidneys subjected to ischemia-reperfusion injury (IRI). Increased expression of SSAT in vitro leads to alterations in cellular polyamine content, depletion of cofactors and precursors of polyamine synthesis, and reduced cell proliferation. In our model system, a >28-fold increase in SSAT levels in HEK-293 cells leads to depletion of polyamines and elevation in the enzymatic activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, suggestive of a compensatory reaction to increased polyamine catabolism. Increased expression of SSAT also led to DNA damage and G2 arrest. The increased DNA damage was primarily due to the depletion of polyamines. Other factors such as increased production of H2O2 due to polyamine oxidase activity may play a secondary role in the induction of DNA lesions. In response to DNA damage the ATM/ATR → Chk1/2 DNA repair and cell cycle checkpoint pathways were activated, mediating the G2 arrest in SSAT-expressing cells. In addition, the activation of ERK1 and ERK2, which play integral roles in the G2/M transition, is impaired in cells expressing SSAT. These results indicate that the disruption of polyamine homeostasis due to enhanced SSAT activity leads to DNA damage and reduced cell proliferation via activation of DNA repair and cell cycle checkpoint and disruption of Raf → MEK → ERK pathways. We propose that in kidneys subjected to IRI, one mechanism through which increased expression of SSAT may cause cellular injury and organ damage is through induction of DNA damage and the disruption of cell cycle.

Xanthine oxidoreductase in respiratory and cardiovascular disorders

2008 ◽  
Vol 294 (5) ◽  
pp. L830-L840 ◽  
Author(s):  
Adel Boueiz ◽  
Mahendra Damarla ◽  
Paul M. Hassoun
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Acute Lung Injury ◽  
Cardiovascular Diseases ◽  
Large Scale ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cardiovascular Disorders ◽  
Xanthine Oxidoreductase

In addition to its critical role in purine metabolism, xanthine oxidoreductase (XOR) has been implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders such as acute lung injury, ischemia-reperfusion injury, atherosclerosis, heart failure, and arterial hypertension. Although much remains to be clarified about the regulation and signaling pathways of this enzyme, it is quite evident from abundant investigation in animal models and some human trials that XOR inhibition can favorably alter critical disease processes and impact outcomes. From promising bench-to-bedside data, a better understanding of this enigmatic enzyme is emerging. However, the positive findings related to XOR inhibition need to be confirmed in large-scale, well-designed clinical trials. This will hopefully provide new opportunities for therapeutic intervention. This article reviews the available evidence involving XOR in oxidative states with specific emphasis on respiratory and cardiovascular diseases.

Abstract 652: Coronary Capillaries in Ischemic Congestive Heart Failure in Rats Exhibit Significant Morphological Disorder

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Heather J Kagan ◽  
Jiqiu Chen ◽  
Peter Backeris ◽  
Irene C Turnbull ◽  
Kevin D Costa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Circular Statistics ◽  
Coronary Artery Ligation ◽  
Sem Images ◽  
Artery Ligation ◽  
Ischemic Congestive Heart Failure

In ischemic congestive heart failure (CHF), the heart is damaged and undergoes compensatory remodeling, a pathological process associated with harmful effects. The goal of this study is to explore the manifestation of CHF by examining the morphological changes occurring in the coronary microvasculature in CHF versus normal rat hearts. We tested the hypothesis that coronary capillaries in rats with CHF exhibit significantly more morphological disorder than those in control rats. Methods: CHF was induced by aortic banding, ischemia/reperfusion injury two months post-banding (left coronary artery ligation for 30 minutes) and aortic debanding one month post-injury. Resin polymer containing fluorescent dye was injected into coronary vasculature of excised hearts. Muscle tissue was digested using NaOH to reveal vascular casts that were sputter coated with gold for imaging under a Scanning Electron Microscope (SEM). A total of 93 SEM images from 14 rats (7 control, 7 CHF) were analyzed for structural alignment using an automated gradient detection algorithm and circular statistics implemented using MATLAB software; Mean Vector Length (MVL) was calculated for each image as a measure of capillary organization (0<MVL<0. MVL->1 perfect alignment, MVL->0 random disarray). Results: CHF capillaries exhibit significantly more structural disorder than control (MVL 0.35±0.02 for 61 CHF, 0.58±0.02 for 32 control. p<0.01). Conclusions: Coronary capillaries in CHF rats exhibit significant abnormal morphological disarray that may impair blood flow hemodynamics and material and oxygen exchange in myocytes. Such disordered capillary remodeling could have detrimental consequences for the progression and prognosis of heart failure.

scholarly journals Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis

2021 ◽  
Vol 16 (1) ◽  
pp. 537-543
Author(s):  
Mei Zhang ◽  
Jing Yuan ◽  
Rong Dong ◽  
Jingjing Da ◽  
Qian Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Tubular Injury ◽  
Jnk Pathway ◽  
Pathway Activation

Abstract Background Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. Methods Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. Results Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. Conclusion Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.

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