Angiotensin II Increases Apoptosis and Caspase-1 Expression in Human Myocardium

2000 ◽  
Vol 6 (S2) ◽  
pp. 630-631
Author(s):  
H. Song ◽  
S. W. Downing ◽  
C. Wei
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Cardiomyocyte Apoptosis ◽  
Tunel Staining ◽  
Caspase 1 ◽  
Potent Vasoconstrictor ◽  
Human Cardiac Tissue

Angiotensin II (AII) is a potent vasoconstrictor and mitogenic factor. The biological actions of All through AII receptors which include AT-1 and AT-2 receptors. However, the effects of AII on cardiomyocyte apoptosis and caspase expression remain controversial. Therefore, the current study was designed to investigate the actions of AII on human cardiomyocyte apoptosis and caspase-1 expression.Human cardiac tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced and incubated in the special tissue culture system for 24 hours in the absence or presence of AII (10-7 M). These studies were repeated with losartan (10-6 M, AT-1 receptor antagonist) and PD123319 (PD, 10-6 M, AT-2 receptor antagonist). To detect the DNA fragmentation, TUNEL staining and DNA gel analyses were performed. The caspase-1 expression was determined by immunohistochemical staining (IHCS). An average of 1000 nuclei was analyzed for both TUNEL and caspase-1 IHCS studies.

The Action of C-Type Natriuretic Peptide on Apoptosis and P53 Expression in Human Cardiomyocytes

2000 ◽  
Vol 6 (S2) ◽  
pp. 622-623
Author(s):  
K. Seta ◽  
Y. Matsuda ◽  
C. Wei
Keyword(s):  
Natriuretic Peptide ◽  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Severe Congestive Heart Failure ◽  
P53 Expression ◽  
Human Cardiomyocytes ◽  
Human Cardiac Tissue ◽  
Apoptosis Related Gene

C-type natriuretic peptide (CNP) is endothelial cell origin and has potent vasodilatory and antimitogenic actions. We reported that CNP was markedly increased in human cardiac tissue with severe congestive heart failure. To date, the effects of CNP on cardiomyocyte growth and death remain unclear. Therefore, the present study was designed to investigate the actions of CNP on apoptosis and apoptosis-related gene p53 expression in human cardiomyocytes.Human cardiac atrial tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced and incubated in the special tissue culture system in the absence or presence of CNP (10-7 M) for 24 hours. These studies were repeated with HS-142-1 (HS, 10-6 M), a natriuretic peptide biological receptor antagonist. To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. The p53 expression was determined by immunohistochemical staining (IHCS). An average of 1000 nuclei was analyzed for TUNEL and p53 staining studies.

scholarly journals Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Al-Forkan ◽  
Fahmida Binta Wali ◽  
Laila Khaleda ◽  
Md. Jibran Alam ◽  
Rahee Hasan Chowdhury ◽  
...  
Keyword(s):  
Heart Surgery ◽  
Cardiac Tissue ◽  
Tissue Injury ◽  
Open Heart Surgery ◽  
Inorganic Arsenic ◽  
Vital Role ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Adjusted Analysis ◽  
Diabetes Status

AbstractInorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P = 0.028), nail (529.29 ± 38.76 ppb, P < 0.05) and cardiac tissue (4.83 ± 0.50 ppb, P < 0.05) samples. Patients’ age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017–8.012, P = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032–3.249, P = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients’ disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA (P = 0.012) and AG (P = 0.034) genotypes and cardiac iAs concentration with AA (P = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280–138.845, P = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065–310.757, P = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325–108.674, P = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280–138.845, P = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.

The Apoptotic Effect of Angiotensin II in Human Vascular Smooth Muscle Cells

2000 ◽  
Vol 6 (S2) ◽  
pp. 636-637
Author(s):  
E. Ou ◽  
C. Wei
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Vascular Smooth Muscle Cells ◽  
Artery Bypass ◽  
Muscle Cells ◽  
Tunel Staining ◽  
Apoptotic Effect

Angiotensin II is a potent vasoconstrictor and mitogenic factor. However, the effects of angiotensin II on human vascular smooth muscle cells apoptosis remain controversial. Therefore, the current study was designed to investigate the actions of angiotensin II on human vascular smooth muscle cells apoptosis.Human saphenous vein was obtained from coronary artery bypass surgery (n=6) and was minced and incubated in the special tissue culture system in the absence or presence of angiotensin II (10-6 to 10-12M) for 1, 2, 4, 8, 16, & 24 hours. These studies were repeated with losartan (10-6M, AT- 1 receptor antagonist) and PD-123319 (10-6M, AT-2 receptor antagonist). To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA agarose gel analyses were performed. An average of 1000 nuclei was analyzed for TUNEL studies.TUNEL staining and DNA gel analysis demonstrated that angiotensin II increased apoptosis in human vascular smooth muscle cells.

Expression of Angiotensin II Type 1 and Type 2 Receptor in Human Myocardium with Congestive Heart Failure

2000 ◽  
Vol 6 (S2) ◽  
pp. 618-619
Author(s):  
P. Y. Lau ◽  
M. G. Cardarelli ◽  
C. Wei
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Human Myocardium ◽  
Receptor Expression ◽  
At2 Receptors

Angiotensin II (AH) is a potent vasoconstrictor and mitogenic factor. AH receptors include type 1 (ATI) and type 2 (AT2) receptors. Recent studies demonstrated that both ATI and AT2 receptors expressed in human myocardium. Circulating and local tissue level of AH was increased in severe congestive heart failure (CHF). However, the expression of ATI and AT2 in cardiac tissue with CHF remains controversial. Therefore, the present study was designed to investigate the protein expression of ATI and AT2 receptors in normal human myocardium and in human cardiac tissue with mild and severe CHF.Human atrial tissues from normal subjects and CHF patients with ischemic cardiomyopathy and dilated cardiomyopathy were obtained from open-heart surgery and cardiac transplantation. ATI and AT2 receptor expression was investigated by immunohistochemical staining (IHCS). The results of IHCS was evaluated by IHCS staining density scores (0, no staining; 1, minimal staining; 2, mild staining; 3, moderate staining; and 4, strong staining).

scholarly journals Cardiomyocyte apoptosis and duration of aortic clamping in pig model of open heart surgery☆☆☆

2006 ◽  
Vol 30 (3) ◽  
pp. 480-484 ◽  
Author(s):  
M MALMBERG ◽  
T VAHASILTA ◽  
A SARASTE ◽  
V KYTO ◽  
J KISS ◽  
...  
Keyword(s):  
Heart Surgery ◽  
Open Heart Surgery ◽  
Cardiomyocyte Apoptosis ◽  
Pig Model ◽  
Open Heart ◽  
Aortic Clamping

scholarly journals Ticagrelor alleviates sepsis-induced myocardial injury via an adenosine-dependent pathway in a mouse sepsis model

2020 ◽  
Vol 43 (4) ◽  
pp. E44-55
Author(s):  
Shengxing Tang ◽  
Cong Fu ◽  
Qiancheng Xu ◽  
Wenjun Guo ◽  
Yuhan Cao
Keyword(s):  
Western Blot ◽  
Protective Effect ◽  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Myocardial Injury ◽  
Cardiomyocyte Apoptosis ◽  
Tunel Staining ◽  
Myocardial Tissue ◽  
Adenosine Receptor Antagonist ◽  
Tnf Α

Purpose: The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury. Methods: The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue. Results: The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR. Conclusion: The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.

Evaluation of Cardiomyocyte Viability after Cardiac Tissue Incubated in Special Culture System

2000 ◽  
Vol 6 (S2) ◽  
pp. 620-621
Author(s):  
C. Wei ◽  
J Papadimitriou
Keyword(s):  
Culture System ◽  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Culture Conditions ◽  
Culture Period ◽  
Open Heart ◽  
Hypertrophic Response ◽  
Signaling Mechanisms ◽  
Apoptotic Effect

Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. We recently developed the new special tissue culture system to culture minced cardiac tissue and to evaluate the apoptotic effect of different agent in cardiomyocytes. After 24 hours culture period, different culture conditions and factors may damage the cardiomyocyte. Therefore, we performed different methods to evaluate the viability of cardiomyocyte in cardiac tissue with 24 hours culture period in our special culture system.Human cardiac atrial tissue was obtained from open-heart surgery (n=6). After cardiac tissue excision, the samples were immediately placed in oxygenated, nominally Ca2+-free Tyrode solution for transport to the laboratory. The time between excision and the beginning of laboratory processing was five to fifteen minutes.

Effect of angiotensin II on primary cardiac fibroblast matrix metalloproteinase activities

Perfusion ◽  
2007 ◽  
Vol 22 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Laura Buford Stacy ◽  
Qianli Yu ◽  
Katherine Horak ◽  
Douglas F Larson
Keyword(s):  
Angiotensin Ii ◽  
Heart Surgery ◽  
Ventricular Dysfunction ◽  
Cardiac Fibroblasts ◽  
Open Heart Surgery ◽  
Left Ventricular ◽  
Enzymatic Activities ◽  
Open Heart ◽  
Ang Ii ◽  
Angiotensin Ii Receptor

Left ventricular dysfunction is associated with reperfusion injury occurring during open-heart surgery. There is an increased secretion of angiotensin II (Ang II) and increased matrix metalloproteinases (MMPs) activities associated with open-heart surgery that may affect the cardiac extracellular matrix (ECM). The goal of this study was to determine the effects of Ang II and selective angiotensin II receptor (AT1-R and AT2-R) blockers on the enzymatic activities of MMPs in primary adult murine cardiac fibroblasts (CF). Our hypothesis is that Ang II, with and without a selective receptor blocker, differentially affects CF MMPs activities. The CF were treated with Ang II (10-6 M) and doses of AT1-R and AT2-R blockers (losartan and PD123319, respectively) at doses of 10-7 to 10-5 M for 48 hours. The Ang IIstimulated CF reduced collagenase activities by only 24% (p =0.004); however, the MMP-2 and MMP-9 gelatinase activities were reduced by 42% and 39%, respectively (p =0.022). The losartan dose dependently increased MMP-2 (p =0.02) and MMP-9 (ns). PD123319 at 10-5 M significantly reduced MMP-2 and MMP-9 activities compared with the Ang II group (p =0.014 and p =0.02, respectively). The doses of PD123319 at 10-6 and 10-7 M increased the MMP-2 and MMP-9 enzymatic activities significantly above the Ang II only group. Thus, Ang II and AT1-R and AT2-R differentially affect the collagenase and gelatinase MMPs activities released by cardiac fibroblasts. Perfusion (2007) 22, 51-55.

scholarly journals Preservation of Myocardial Perfusion and Function by Keeping Hypertrophied Heart Empty and Beating for Valve Surgery: An In Vivo MR Study of Pig Hearts

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jian Wang ◽  
Bo Xiang ◽  
Jixian Deng ◽  
Hung-Yu Lin ◽  
Darren H. Freed ◽  
...  
Keyword(s):  
Myocardial Perfusion ◽  
Caspase 3 ◽  
Heart Surgery ◽  
Troponin I ◽  
Contractile Function ◽  
Open Heart Surgery ◽  
Left Ventricular ◽  
Cine Mri ◽  
Tunel Staining ◽  
Sham Operation

Objectives. Normothermic hyperkalemic cardioplegia arrest (NHCA) may not effectively preserve hypertrophied myocardium during open-heart surgery. Normothermic normokalemic beating perfusion (NNBP), keeping hearts empty-beating, was utilized as an alternative to evaluate its cardioprotective role.Materials and Methods. Twelve hypertrophied pig hearts at 58.6 ± 7.2 days after ascending aorta banding underwent NNBP and NHCA, respectively. Near infrared myocardial perfusion imaging with indocyanine green (ICG) was conducted to assess myocardial perfusion. Left ventricular (LV) contractile function was assessed by cine MRI. TUNEL staining and western blotting for caspase-3 cleavage and cardiac troponin I (cTnI) degradation were conducted in LV tissue samples.Results. Ascending aortic diameter was reduced by52.7%±0.4%at approximately fifty-eight days after banding. LV wall thickness was significantly higher in aorta banding than in sham operation. Myocardial blood flow reflected by maximum ICG absorbance value was markedly higher in NNBP than in NHCA. The amount of apoptotic cardiomyocyte was significantly lower in NNBP than in NHCA. NNBP alleviated caspase-3 cleavage and cTnI degradation associated with NHCA. NNBP displayed a substantially increased postoperative ejection fraction relative to NHCA.Conclusions. NNBP was better than NHCA in enhancing myocardial perfusion, inhibiting cardiomyocyte apoptosis, and preserving LV contractile function for hypertrophied hearts.

Effect of INS50589, a Reversible ADP-Receptor Antagonist, on Platelet Function and Blood Loss in a Canine Model of Cardiopulmonary Bypass.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2172-2172
Author(s):  
Arthur P. Bode ◽  
Christopher S. Crean ◽  
You-Su Sun ◽  
Wiley Nifong ◽  
Jose L. Boyer ◽  
...  
Keyword(s):  
Treatment Group ◽  
Blood Loss ◽  
Receptor Antagonist ◽  
Platelet Function ◽  
Whole Blood ◽  
Heart Surgery ◽  
Ex Vivo ◽  
Open Heart Surgery ◽  
Canine Model ◽  
Open Heart

Abstract Open-heart surgery performed with cardiopulmonary extracorporeal bypass (CPB) of anticoagulated blood often is complicated by excessive postoperative hemorrhage due to an acquired platelet function defect and thrombocytopenia inherent to the procedure. One strategy for reducing excessive blood loss is to protect the platelets pharmacologically from activation and damage during the surgical procedure and the CPB, but most inhibitors of platelet activation used in this way would exacerbate bleeding because of the duration of their effect. INS50589 is a competitive and selective P2Y12 receptor antagonist in development by Inspire Pharmaceuticals Inc. Previous studies in normal dogs indicate that 20μM ADP induced ex vivo whole blood platelet aggregation is completely inhibited by the administration of INS50589 and that the effect is quickly reversed upon discontinuation of the administration. This drug is now being tested for efficacy and safety in a canine model of CPB established at East Carolina University. Subjects in the range of 20–30 kg are prepared by sternotomy for extracorporeal recirculation of blood after systemic heparinization. CPB occurs for ninety minutes, followed by weaning from the pump and maintenance for a four hour postoperative period. INS50589 was administered by continuous infusion at a rate of 17 mg/kg/min at initiation of sternotomy and throughout CPB until weaned. Special testing in all subjects includes ex vivo whole blood aggregometry with two doses of ADP, thromboelastography with the TEG® ADP Mapping kit, bleeding times using a 23 gauge puncture of the exposed jugular vein, and measurements of blood loss from the surgical fields. In the placebo treated group, there was a significant loss of platelet response to ADP during CPB that remained in the post-op period at approx 50% of initial values; in contrast, the drug-treated subjects show post-op recovery of ADP response to within 90% of initial values (p<0.01). The vessel bleeding time (VBT) within both groups was greatly prolonged during CPB. Preliminary analysis suggests that in the post-operative period the VBT returned to baseline values after the infusion was discontinued; however, the return was faster in the INS50589-treated animals when compared with the placebo group. The volume of post-operative blood loss was variable but appears to be less in the drug-treatment group versus placebo controls. When adjusted on the basis of red cell mass in the shed blood per body weight the difference was significant (4.78±1.99e10 vs. 10.1±2.91e10 red blood cells/kg), p <0.05. Other preliminary findings in the treatment group included a lesser CPB-related decrease in platelet count, a higher average hematocrit, higher post-op fibrinogen concentration, and a more stable post-op course. These preliminary findings suggest that INS50589 should be effective in protecting platelet function and reducing blood loss in human patients undergoing open-heart surgery.

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