scholarly journals Expression and Signaling of β-Adrenoceptor Subtypes in the Diabetic Heart

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2548
Author(s):  
Betul R. Erdogan ◽  
Martin C. Michel ◽  
Ebru Arioglu-Inan

Diabetes is a chronic, endocrine disorder that effects millions of people worldwide. Cardiovascular complications are the major cause of diabetes-related morbidity and mortality. Cardiac β1- and β2-adrenoceptor (AR) stimulation mediates positive inotropy and chronotropy, whereas β3-AR mediates negative inotropic effect. Changes in β-AR responsiveness are thought to be an important factor that contributes to the diabetic cardiac dysfunction. Diabetes related changes in β-AR expression, signaling, and β-AR mediated cardiac function have been studied by several investigators for many years. In the present review, we have screened PubMed database to obtain relevant articles on this topic. Our search has ended up with wide range of different findings about the effect of diabetes on β-AR mediated changes both in molecular and functional level. Considering these inconsistent findings, the effect of diabetes on cardiac β-AR still remains to be clarified.

2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.


2020 ◽  
Vol 20 (14) ◽  
pp. 1310-1323
Author(s):  
Andrea Bosso ◽  
Antimo Di Maro ◽  
Valeria Cafaro ◽  
Alberto Di Donato ◽  
Eugenio Notomista ◽  
...  

Host defence peptides (HDPs) are powerful modulators of cellular responses to various types of insults caused by pathogen agents. To date, a wide range of HDPs, from species of different kingdoms including bacteria, plant and animal with extreme diversity in structure and biological activity, have been described. Apart from a limited number of peptides ribosomally synthesized, a large number of promising and multifunctional HDPs have been identified within protein precursors, with properties not necessarily related to innate immunity, consolidating the fascinating hypothesis that proteins have a second or even multiple biological mission in the form of one or more bio-active peptides. Among these precursors, enzymes constitute certainly an interesting group, because most of them are mainly globular and characterized by a fine specific internal structure closely related to their catalytic properties and also because they are yet little considered as potential HDP releasing proteins. In this regard, the main aim of the present review is to describe a panel of HDPs, identified in all canonical classes of enzymes, and to provide a detailed description on hydrolases and their corresponding HDPs, as there seems to exist a striking link between these structurally sophisticated catalysts and their high content in cationic and amphipathic cryptic peptides.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Foulkes ◽  
B Costello ◽  
E.J Howden ◽  
K Janssens ◽  
H Dillon ◽  
...  

Abstract Background Young cancer survivors are at increased risk of impaired cardiopulmonary fitness (VO2peak) and heart failure. Assessment of exercise cardiac reserve may reveal sub-clinical abnormalities that better explain impairments in fitness and long term heart failure risk. Purpose To investigate the presence of impaired VO2peak in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac reserve Methods Twenty pediatric cancer survivors (aged 8–24 years) treated with anthracycline chemotherapy underwent cardiopulmonary exercise testing to quantify VO2peak, with a value <85% of predicted defined as impaired VO2peak. Resting cardiac function was assessed using 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate (HR), stroke volume index (SVi) and cardiac index (CI) using exercise cardiac magnetic resonance imaging. Results 12 of 20 survivors (60%) had impaired VO2peak (97±14% vs. 70±16% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired VO2peak. However, those with reduced VO2peak had diminished cardiac reserve, with a lesser increase in CI (Fig. 1A) and SVi (Fig. 1B) during exercise (Interaction P=0.001 for both), whilst the HR response was similar (Fig. 1C; P=0.71). Conclusions Resting measures of cardiac function are insensitive to significant cardiac dysfunction amongst pediatric cancer survivors with reduced VO2peak. Measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation


Author(s):  
Kendrick Lee ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.


2021 ◽  
Author(s):  
Sanne M. Snelder ◽  
Yaar Aga ◽  
Lotte E. de Groot-de Laat ◽  
L. Ulas Biter ◽  
Manuel Castro Cabezas ◽  
...  

Author(s):  
Florin Stamatian ◽  
Gabriela Caracostea

ABSTRACT Background Although it is known that cardiac parameters have abnormal values in severely affected fetuses with intrauterine growth restriction (IUGR), recent research suggested that subclinical cardiac dysfunction may be present from the early stages of fetal deterioration. The identification and monitoring of cardiac dysfunction may be relevant for the management of these cases. Materials and methods In this prospective observational study, we evaluated 17 IUGR fetuses from nulliparous pregnant women diagnosed with pre-eclampsia. Cardiac structural assessment was performed using segmental sequential analysis. Cardiac function was assessed by conventional echocardiography and Tissue Doppler Imaging (TDI). Results Gestational age at admittance ranged between 24 and 30 weeks. A severe form of pre-eclampsia was diagnosed in 2 of 17 cases. Conventional cardiac examination showed low left and right ventricular diastolic filling with low E and A velocities, and increased myocardial performance indexes for both ventricles. Using TDI we observed decreased myocardial velocities and impaired contractility (demonstrated by low left and right diastolic velocities, as well as increased E’/A’ ratios). Conclusion Our study confirms the presence of early cardiac dysfunction in IUGR fetuses. Further studies are warranted to confirm the utility of TDI in obstetric ultrasound routine examination for monitoring fetal cardiac function in high-risk pregnancies. How to cite this article Caracostea G, Stamatian F. Assessment of Cardiac Dysfunction in the Intrauterine Growthrestricted Fetuses from Pre-eclamptic Mothers. Donald School J Ultrasound Obstet Gynecol 2014;8(2):123-127.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Makiko Miyata ◽  
Satoshi Suzuki ◽  
Tomofumi Misaka ◽  
Shu-ichi Saitoh ◽  
Yasuchika Takeishi

Background: Senescence marker protein 30 (SMP30) was originally identified as an aging marker protein in the rat liver. The expression of SMP30 decreases with aging androgen-independently. Doxorubicin (DOX) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. SMP30 may have anti-oxidative and anti-apoptosis functions in several organs, but functional role of SMP30 has not been rigorously examined in the heart. We hypothesized that SMP30 has cardio-protective function by anti-aging and anti-oxidant effects on DOX-induced cardiac dysfunction. Method and Results: Male SMP30 knockout (SMP30KO) and age-matched littermate male wild-type (WT) mice at 12-14 weeks of age were given intraperitoneal injections of DOX (20 mg/kg) or saline. Seven days after DOX injection, echocardiography revealed that left ventricular ejection fraction in DOX-treated SMP30KO mice was more severely reduced than in DOX-treated WT mice (40.9 ± 3.1% vs. 46.9 ± 4.9%, P<0.01). Morphological examination of myocardial sections showed fibrotic change in DOX-treated SMP30KO mice significantly increased compared to DOX-treated WT mice (3.2 ± 0.5% vs. 1.3 ± 0.2%, P<0.01). Generation of reactive oxygen species assessed by dihydroethidium staining was greater in DOX-treated SMP30KO mice than DOX-treated WT mice (166.9 ± 8.6% vs. 131.6 ± 5.8%, P<0.01). Moreover, apoptotic signaling pathways such as caspase-3 activity (1.8 ± 0.1% vs. 1.1 ± 0.2%, P<0.01), bax/bcl-2 ratio (2.4 ± 0.3% vs.1.6 ± 0.2%, P<0.05) and phosphorylation activity of c-Jun N-terminal kinase (1.6 ± 0.3 vs. 1.0 ± 0.1, P<0.05) were significantly elevated in the SMP30KO mice compared with WT mice after DOX injection. The numbers of TUNEL-positive nuclei in the myocardium were higher in DOX-treated SMPKO mice than in DOX-treated WT mice (0.15 ± 0.02% vs. 0.08 ± 0.01%, P<0.01). Conclusions: The results of this study demonstrated that DOX-induced cardiotoxicity is aggravated in SMP30KO mice by exacerbating of superoxide generation, leading to enhanced apoptosis of cardiomyocytes. SMP30 has a cardio-protective role by anti-apoptotic and anti-oxidative effects in DOX-induced cardiotoxicity.


Author(s):  
Abdul Nasir ◽  
Atif Ali Khan Khalil ◽  
Muhammad Zeeshan Bhatti ◽  
Ashfaq Ur Rehman ◽  
Jiayi Li ◽  
...  

: Persicaria hydropiper (L.) Delarbre (family Polygonacea), commonly known as Polygonum hydropiper, is a popular medicinal plant used in traditional medicine. The plant is indigenous to the tropical northern hemisphere and temperate zone including China, Bangladesh, India, and Japan. The plant is used in folk medicine for numerous ailments such as hemorrhoids, antifertility, diarrhea, and dyspepsia. Its medicinal usage in Unani, Ayurveda, Siddha, and other traditional medicine is well-recognized. So far, a wide range of active phytochemicals of this plant has been identified, such as flavonoids, sulphated flavonoids, terpenoids, anthraquinones, steroids, coumarin, simple phenolics, and others. Pharmacological data reported in the literature suggest that various parts of P. hydropiper exhibit antimicrobial, antioxidant, hypoglycemic, antidepressant, cardioprotective, hepatoprotective, anticancer, and antifertility effects. The present review aim is to compile the coherently document research on the phytochemical, pharmacological, and biological activities of P. hydropiper from different parts of the globe.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Simon Stewart ◽  
Melinda Carrington ◽  
Yih Kai Chan ◽  
Garry Jennings ◽  
Chiew Wong ◽  
...  

Background: The natural history of chronic heart failure (CHF) is characterized by initial cardiac insult and/or stressors over time that leaves affected individuals at high risk for progressive cardiac dysfunction and eventual development of the syndrome. Methods: Of a total of 624 subjects at high risk of developing CHF randomized into the NIL-CHF Study comparing a hybrid program of home and clinic-based follow-up (NIL-CHF group) to Standard Care, 454 (73%) underwent serial echocardiography at 1 month post index cardiac hospitalization and at 3 years. At both time points (nil signs/symptoms of CHF at baseline), these were blindly classified as follows: 1) no cardiac abnormality, 2) systolic dysfunction/HFrEF - LVEF ≤ 45% ), 3) diastolic dysfunction/HFpEF as defined by any moderate diastolic dysfunction (with pseudonormalization pattern) or E/E prime ratio ≥ 15, 4) combination of 2 & 3 and 5) other cardiac abnormality (including LVH). Pre-specified criteria were used to determine - i) no change, ii) improvement or iii) deterioration in cardiac function from baseline to 3 years. Results: Mean age was 66±11 years, 71% were male, 70% were hospitalized with an acute coronary syndrome and 62% and 26%, respectively, were being treated for hypertension and diabetes. At baseline 25.2% vs. 28.4% (p=ns), 15.1% vs. 9.1% (p<0.05), 35.1% vs. 32.4% (p=ns) and 34.3% vs. 39.6% had normal cardiac function, HFrEF, HFpEF (13% both HFrEF and HFpEF overall) and LVH (the predominant “other” cardiac abnormality), respectively. At 3 years the proportion of subjects with reversal of pre-existing HFrEF or HFpEF was lower in the NIL-CHF group (23% vs. 16%; p=0.063). Moreover, significantly more NIL-CHF subjects demonstrated any form of cardiac recovery/reversal on echocardiography (39% vs. 25%, p=0.011, 95% CI 1.35, 95% CI 1.04, 1.76). They also demonstrated significantly greater regression to normal LV structure (36% vs. 25%; p=0.047) among those with LVH at baseline. Conclusions: These pre-specified analyses (secondary endpoint) of the recently completed NIL-CHF Study suggests a cardio-protective effect conferred by a long-term, nurse-led, home and clinic-based intervention targeting hospitalized individuals at high risk for developing CHF.


Sign in / Sign up

Export Citation Format

Share Document