scholarly journals Expression and roles of N-type Ca channel in cardiaomyocytes

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Kobara ◽  
H Toba ◽  
T Nakata
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Myocytes ◽  
Caspase 3 ◽  
Cardiac Tissue ◽  
Pathological Condition ◽  
Ca Channel ◽  
Myocyte Apoptosis ◽  
Ldh Release ◽  
Cultured Cardiomyocytes

Abstract Background Voltage dependent Ca channels are divided to L-, T-, N-, P/Q-, and R-types, and N-type Ca channel (NCC) is mainly expressed in nerve terminal and regulates neurotransmitter release. Recently, NCC has been reported to express in adrenal gland and renal tubular cells. We examined whether NCC is expressed in cardiac myocytes and if so, the roles of this channel. Methods Expression of NCC mRNA and protein in cardiomyocytes were assessed by quantitative real time PCR and Western blot analysis using neonatal rat cultured cardiomyocytes, infant, and adult rat hearts. Expression site of NCC in cardiomyocytes was examined by confocal imaging of immunofluorescent staining. The roles of NCC in physiological Ca transient in neonatal myocytes were examined using fluorescence imaging of Fluo4, an intracellular Ca indicator. To examine the effects of pathological condition, such as heart failure and ischemia-reperfusion, on NCC expression, cultured cardiomyocytes were treated with norepinephrine (10 μmol/L, 24 hours) or subjected to 5 hours of hypoxia followed by 30 minutes of reoxygenation. In addition, adult rats were subjected to myocardial infarction by ligating the left anterior coronary artery. Lethal myocyte injury was examined by LDH activity in culture medium and myocyte apoptosis was examined by nuclear staining with DAPI and caspase 3 activity. To clarify the roles of NCC in neonatal myocytes in these pathological conditions, we examine the effect of ω-conotoxin, a selective NCC blocker. Results NCC mRNA and protein were expressed in neonatal cardiomyocytes. Immunocytochemical staining showed NCC was expressed in myocyte plasma membrane. During physiological spontaneous beating, ω-conotoxin did not affect beating rate and intra cellular Ca transient, suggesting that the roles of NCC on physiological beating are little. After birth level of NCC mRNA expression in cardiac tissue gradually decreased within 2 weeks and low level of mRNA expressed continuously in adult cardiac tissue. However, in pathological condition, mRNA and protein levels of NCC in non-infarcted region were increased 4 weeks after myocardial infarction. In addition, hypoxia-reoxygenation and norepinephrine administration increased LDH release and myocyte apoptosis in association with increase in NCC expression in neonatal cultured myocytes. ω-conotoxin significantly suppressed hypoxia/reoxygenation- and norepinephrine-induced LDH release and caspase 3 activation. Conclusion NCC is expressed in neonatal cardiac myocytes and the expression level was decreased after birth. Pathological condition, such as ischemic heart disease and heart failure, upregulated NCC expression in cardiomyocytes and NCC exacerbated lethal myocyte injury, while roles of NCC in physiological beating are little. FUNDunding Acknowledgement Type of funding sources: None.

Administration of Tauroursodeoxycholic Acid (TUDCA) Reduces Apoptosis Following Myocardial Infarction in Rat

2007 ◽  
Vol 35 (02) ◽  
pp. 279-295 ◽  
Author(s):  
Andrew L. Rivard ◽  
Clifford J. Steer ◽  
Betsy T. Kren ◽  
Cecilia M. P. Rodrigues ◽  
Rui E. Castro ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Caspase 3 ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Black Bear ◽  
Recent Analysis ◽  
Major Constituent ◽  
Tauroursodeoxycholic Acid ◽  
Cellular Effects ◽  
Infarct Area

Black bear bile has been used in traditional Chinese medicine to treat liver and eye related illnesses for centuries. A major constituent of bile is ursodeoxycholic acid (UDCA). Recent analysis of the cellular effects of UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) have demonstrated their antiapoptotic properties through regulation of Bcl-2 family and survival signaling proteins (Bax, Bad, phosphatidylinositol-3-kinase). In this study, we tested the hypothesis that TUDCA administered to rats prior to a myocardial infarction (MI) would exhibit anti-apoptotic effects and improve cardiac function. Prior to ligation of the left anterior descending (LAD) coronary artery, TUDCA (50 mg/ml, 400 mg/kg, IV) or PBS was administered to rats. Animals were sacrificed 24 hours after ligation for terminal transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and caspase-3 activity to assess apoptosis. Additional TUDCA or PBS treated rats underwent pre-operative,1 and 4 week transthoracic ultrasounds to assess heart function by quantification of shortening fraction (SF) and infarct area. TUNEL labeling of the cardiac tissue revealed a significant reduction in apoptotic cells in rats given TUDCA prior to ischemic injury ( p = 0.05). In support of reducing apoptosis, caspase-3 activity in the TUDCA treated animals also decreased ( p = 0.02). By 4 weeks, a significantly smaller infarct area was present in the TUDCA group compared to the PBS group (0.05 vs. 0.13 cm2, p = NS) and there was also an improvement in SF. The results provide evidence for TUDCA as a viable treatment for reducing apoptosis in a model of myocardial infarction. Additional studies will distinguish the functional result of improved cell survival following infarction, suggesting the potential for clinical application of this anti-apoptotic drug in treatment of acute MI.

scholarly journals Coronary microvascular dysfunction in hypertrophy and heart failure

2020 ◽  
Vol 116 (4) ◽  
pp. 806-816 ◽  
Author(s):  
Paolo G Camici ◽  
Carsten Tschöpe ◽  
Marcelo F Di Carli ◽  
Ornella Rimoldi ◽  
Sophie Van Linthout
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Pathological Condition ◽  
Microvascular Dysfunction ◽  
Left Ventricular ◽  
Physiological Adaptation ◽  
Coronary Microvascular Dysfunction ◽  
Wall Thickening ◽  
Reduced Ejection Fraction

Abstract Left ventricular (LV) hypertrophy (LVH) is a growth in left myocardial mass mainly caused by increased cardiomyocyte size. LVH can be a physiological adaptation to physical exercise or a pathological condition either primary, i.e. genetic, or secondary to LV overload. Patients with both primary and secondary LVH have evidence of coronary microvascular dysfunction (CMD). The latter is mainly due to capillary rarefaction and adverse remodelling of intramural coronary arterioles due to medial wall thickening with an increased wall/lumen ratio. An important feature of this phenomenon is the diffuse nature of this remodelling, which generally affects the coronary microvessels in the whole of the left ventricle. Patients with LVH secondary to arterial hypertension can develop both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). These patients can develop HFrEF via a ‘direct pathway’ with an interval myocardial infarction and also in its absence. On the other hand, patients can develop HFpEF that can then progress to HFrEF with or without interval myocardial infarction. A similar evolution towards LV dysfunction and both HFpEF and HFrEF can occur in patients with hypertrophic cardiomyopathy, the most common genetic cardiomyopathy with a phenotype characterized by massive LVH. In this review article, we will discuss both the experimental and clinical studies explaining the mechanisms responsible for CMD in LVH as well as the evidence linking CMD with HFpEF and HFrEF.

scholarly journals G Protein–Coupled Receptor Kinase 2 Ablation in Cardiac Myocytes Before or After Myocardial Infarction Prevents Heart Failure

2008 ◽  
Vol 103 (4) ◽  
pp. 413-422 ◽  
Author(s):  
Philip W. Raake ◽  
Leif E. Vinge ◽  
Erhe Gao ◽  
Matthieu Boucher ◽  
Giuseppe Rengo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
G Protein ◽  
Cardiac Myocytes ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

P6275Role of autophagy in imatinib-induced cardiotoxicity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kobara ◽  
N Naseratun ◽  
Y Watanabe ◽  
H Toba ◽  
T Nakata
Keyword(s):  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Cardiac Tissue ◽  
Oxygen Species ◽  
In Vitro Experiments ◽  
In Vivo Experiments ◽  
Myocyte Apoptosis ◽  
Dose Dependent

Abstract Background Cardiotoxicity is one of the severe adverse effects of chemotherapeutic agents. Imatinib, a therapeutic agent for chronic myelogenous leukemia, has been reported to induce cardiotoxicity. Autophagy is an intracellular bulk protein and organelle degradation process, but it is unclear whether autophagy functions as pro-death or pro-survival program during disease conditions. We examined whether imatinib induces myocyte autophagy and the role of autophagy in imatinib-induced cardiotoxicity in in vitro and in vivo experiments. Methods In in vitro experiments, neonatal rat cardiac myocytes were treated with imatinib (1, 5, 10 μM; 1–6 hrs). Inhibition of autophagy was performed using 3-methyl-adenine (3MA), an autophagic inhibitor, and transfection with Atg5-targeted siRNA. Myocyte apoptosis was detected by morphological change in nuclei and caspase 3 activity. Mitochondria-derived reactive oxygen species production was detected using MitoSOX and mitochondrial membrane potential was assessed by TMRM staining. Expressions of cytochrome c in mitochondria and cytosole were examined by Werstern blotting. Myocyte autophagy was assessed by monodansylcadaverine staining and microtubule-associated protein light chain (LC) 3-II expression. In in vivo experiments, C57BL6 mice were treated with imatinib (50 and 200 mg/kg/day) for 5 weeks in the presence or absence of 3MA. Cardiac function was examined by echocardiography. In cardiac tissue, apoptotic myocytes were examined by TUNEL assay and autophagy was examined by LC3-II expression. Results In in vitro experiments, imatinib increased apoptotic nuclei and caspase 3 activity, in a dose-dependent manner. Consequently, imatinib augmented production of mitochondria-derived reactive oxygen species, loss of mitochondrial membrane potential, and the release of cytochrome c from mitochondria to cytosole, suggesting that imatinib induced mitochondrial-apoptotic pathway. On the other hand, imatinib significantly increased monodansylcadaverine stained dots and LC3-II expression, suggesting that imatinib increased autophagy. 3MA and Atg5 siRNA augmented imatinib-induced apoptosis by 60% and 30%, respectively. In in vivo experiments, imatinib (200 mg) exhibited the dilatation of left ventricle by 15% and the depression of left ventricular fractional shortening by 23%. Ratio of apoptotic myocytes was significantly increased and LC3-II expression in cardiac tissue was enhanced by imatinib in a dose-dependent fashion. Co-treatment with 3MA and imatinib further impaired imatinib-induced myocyte apoptosis by 3 fold and LV dysfunction by 20%. Conclusion These results indicate that imatinib induced myocyte apoptosis, leading to cardiac dysfunction. Imatinib enhanced myocyte autophagy as a consequence of apoptosis and autophagy was a beneficial phenomenon in this condition.

scholarly journals The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction

2019 ◽  
Vol 16 (3) ◽  
pp. 612-625 ◽  
Author(s):  
Esther López ◽  
Rebeca Blázquez ◽  
Federica Marinaro ◽  
Verónica Álvarez ◽  
Virginia Blanco ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Vesicles ◽  
Acute Phase ◽  
Peripheral Blood ◽  
Cardiac Tissue ◽  
Troponin I ◽  
Pathological Condition ◽  
Experimental Conditions ◽  
Inflammatory Phase ◽  
Arginase 1

AbstractAcute myocardial infarction triggers a strong inflammatory response in the affected cardiac tissue. New therapeutic tools based on stem cell therapy may modulate the unbalanced inflammation in the damaged cardiac tissue, contributing to the resolution of this pathological condition. The main goal of this study was to analyze the immunomodulatory effects of cardiosphere-derived cells (CDCs) and their extracellular vesicles (EV-CDCs), delivered by intrapericardial administration in a clinically relevant animal model, during the initial pro-inflammatory phase of an induced myocardial infarction. This effect was assessed in peripheral blood and pericardial fluid leukocytes from infarcted animals. Additionally, cardiac functional parameters, troponin I, hematological and biochemical components were also analyzed to characterize myocardial infarction-induced changes, as well as the safety aspects of these procedures. Our preclinical study demonstrated a successful myocardial infarction induction in all animals, without any reported adverse effect related to the intrapericardial administration of CDCs or EV-CDCs. Significant changes were observed in biochemical and immunological parameters after myocardial infarction. The analysis of peripheral blood leukocytes revealed an increase of M2 monocytes in the EV-CDCs group, while no differences were reported in other lymphocyte subsets. Moreover, arginase-1 (M2-differentiation marker) was significantly increased in pericardial fluids 24 h after EV-CDCs administration. In summary, we demonstrate that, in our experimental conditions, intrapericardially administered EV-CDCs have an immunomodulatory effect on monocyte polarization, showing a beneficial effect for counteracting an unbalanced inflammatory reaction in the acute phase of myocardial infarction. These M2 monocytes have been defined as “pro-regenerative cells” with a pro-angiogenic and anti-inflammatory activity.

Surface-modified polymers for cardiac tissue engineering

2017 ◽  
Vol 5 (10) ◽  
pp. 1976-1987 ◽  
Author(s):  
Ambigapathi Moorthi ◽  
Yu-Chang Tyan ◽  
Tze-Wen Chung
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Tissue Engineering ◽  
Causes Of Death ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Modified Polymers ◽  
Surface Modified

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide.

scholarly journals Biomaterial strategies for alleviation of myocardial infarction

2011 ◽  
Vol 9 (66) ◽  
pp. 1-19 ◽  
Author(s):  
Jayarama Reddy Venugopal ◽  
Molamma P. Prabhakaran ◽  
Shayanti Mukherjee ◽  
Rajeswari Ravichandran ◽  
Kai Dan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Left Ventricular ◽  
World Health ◽  
Myocardial Repair ◽  
Apparent Lack

World Health Organization estimated that heart failure initiated by coronary artery disease and myocardial infarction (MI) leads to 29 per cent of deaths worldwide. Heart failure is one of the leading causes of death in industrialized countries and is expected to become a global epidemic within the twenty-first century. MI, the main cause of heart failure, leads to a loss of cardiac tissue impairment of left ventricular function. The damaged left ventricle undergoes progressive ‘remodelling’ and chamber dilation, with myocyte slippage and fibroblast proliferation. Repair of diseased myocardium with in vitro -engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for heart failure patients. These events reflect an apparent lack of effective intrinsic mechanism for myocardial repair and regeneration. Motivated by the desire to develop minimally invasive procedures, the last 10 years observed growing efforts to develop injectable biomaterials with and without cells to treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen, chitosan, self-assembling peptides, biopolymers and a range of synthetic hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to generate biocompatible, non-immunogenic heart muscle with morphological and functional properties similar to natural myocardium to repair MI. This review summarizes the properties of biomaterial substrates having sufficient mechanical stability, which stimulates the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.

Abstract 16402: Epa and Dha Suppressed Myocardial Infarction-induced Systolic Dysfunction by Inhibiting P300 Hat Activity

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Masafumi Funamoto ◽  
Yoichi Sunagawa ◽  
Yasufumi Katanasaka ◽  
Kana Shimizu ◽  
Yusuke Miyazaki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Systolic Dysfunction ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Omega 3 ◽  
Direct Inhibition ◽  
Epa And Dha ◽  
Cultured Cardiomyocytes

Introduction: p300, an intrinsic histone acetyltransferase (HAT), has a crucial role in the pathological cardiac hypertrophy and the development of heart failure in vivo . Although many studies have shown a cardioprotective effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 fatty acids, little is known about the effects of these acids on cardiac hypertrophy. Aim: This study investigated whether EPA and DHA inhibited the development of heart failure in rats with myocardial infarction (MI). Methods and Results: To investigate the effects on cardiomyocyte hypertrophy in cultured cardiomyocytes, neonatal rat cultured cardiomyocytes were stimulated with phenylephrine (PE). EPA or DHA significantly inhibited PE-induced cardiomyocyte hypertrophy. EPA and DHA repressed to the same extent PE-induced acetylation of histone H3 in cultured cardiomyocytes. An in vitro HAT assay was performed to determine the direct inhibition of p300-HAT activity. The results revealed that EPA and DHA significantly inhibited p300-HAT activity. To assess whether EPA and DHA suppress p300-HAT activity directly in cultured cardiomyocytes, p300 was overexpressed in cultured cardiomyocytes. Treatment with EPA or DHA inhibited the overexpression of p300-induced cardiomyocyte hypertrophy in cultured cardiomyocytes. MI-operated rats (FS < 40%) were randomly assigned to 3 groups: vehicle, EPA (1 g/kg) and DHA (1 g/kg). One week after MI operation, oral administrations were repeated for 6 weeks. Echocardiographic analysis demonstrated that EPA and DHA significantly improved MI-induced cardiac dysfunction. In addition, Masson's trichrome staining showed that EPA and DHA inhibit MI-induced fibrosis response in MI rats. EPA and DHA repressed MI-induced hypertrophic response gene transcriptions such as ANF and BNP with RT-PCR. Western blotting demonstrated that inhibited MI-induced H3K9 acetylation in rats . Conclusion: EPA and DHA suppressed hypertrophic responses to the same extent, through the direct inhibition of p300-HAT activity and repressed MI-induced development of heart failure.

scholarly journals A Possible Mechanism behind Faster Clearance and Higher Peak Concentrations of Cardiac Troponin I Compared with Troponin T in Acute Myocardial Infarction

2020 ◽  
Vol 66 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Karin Starnberg ◽  
Vincent Fridén ◽  
Aida Muslimovic ◽  
Sven-Erik Ricksten ◽  
Susanne Nyström ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Cardiac Troponin ◽  
Cardiac Tissue ◽  
Troponin I ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Human Cardiac Tissue

Abstract Background Although cardiac troponin I (cTnI) and troponin T (cTnT) form a complex in the human myocardium and bind to thin filaments in the sarcomere, cTnI often reaches higher concentrations and returns to normal concentrations faster than cTnT in patients with acute myocardial infarction (MI). Methods We compared the overall clearance of cTnT and cTnI in rats and in patients with heart failure and examined the release of cTnT and cTnI from damaged human cardiac tissue in vitro. Results Ground rat heart tissue was injected into the quadriceps muscle in rats to simulate myocardial damage with a defined onset. cTnT and cTnI peaked at the same time after injection. cTnI returned to baseline concentrations after 54 h, compared with 168 h for cTnT. There was no difference in the rate of clearance of solubilized cTnT or cTnI after intravenous or intramuscular injection. Renal clearance of cTnT and cTnI was similar in 7 heart failure patients. cTnI was degraded and released faster and reached higher concentrations than cTnT when human cardiac tissue was incubated in 37°C plasma. Conclusion Once cTnI and cTnT are released to the circulation, there seems to be no difference in clearance. However, cTnI is degraded and released faster than cTnT from necrotic cardiac tissue. Faster degradation and release may be the main reason why cTnI reaches higher peak concentrations and returns to normal concentrations faster in patients with MI.

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