scholarly journals Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Romina Higa ◽  
María Laura Leonardi ◽  
Alicia Jawerbaum
Keyword(s):  
Cardiovascular Diseases ◽  
Fetal Programming ◽  
Fetal Heart ◽  
Experimental Studies ◽  
Adult Life ◽  
Maternal Diabetes ◽  
Matrix Remodeling ◽  
Carbohydrate And Lipid Metabolism ◽  
Target Organs ◽  
Fetal Stage

Maternal diabetes is a prevalent pathology that increases the risk of cardiovascular diseases in the offspring, the heart being one of the main target organs affected from the fetal stage until the adult life. Metabolic, pro-oxidant, and proinflammatory alterations in the fetal heart constitute the first steps in the adverse fetal programming of cardiovascular disease in the context of maternal diabetes. This review discusses both human and experimental studies addressing putative mechanisms involved in this fetal programming of heart damage in maternal diabetes. These include cardiac epigenetic changes, alterations in cardiac carbohydrate and lipid metabolism, damaging effects caused by a pro-oxidant and proinflammatory environment, alterations in the cardiac extracellular matrix remodeling, and specific signaling pathways. Putative actions to prevent cardiovascular impairments in the offspring of mothers with diabetes are also discussed.

Maternal Nutrition and Fetal Programming of the Immune System: Epidemiological and Experimental Evidences

2019 ◽  
pp. 1-8
Author(s):  
Siti Rohaiza Ahmad
Keyword(s):  
Immune System ◽  
Fetal Programming ◽  
Maternal Nutrition ◽  
Negative Impact ◽  
Experimental Studies ◽  
Adult Life ◽  
Experimental Models ◽  
Fetal Life ◽  
Immune Functions ◽  
Immune System Development

Maternal nutrition will not only affects pregnancy outcomes (such as birth weight) but will also affect the state of the fetus in their adult life in terms of diseases occurrence and also immune system development. Inadequate nutrition particularly will have a negative impact on the proliferation of the various cell populations responsible for the immune functions as well as the accumulation of high concentrations of inflammatory components. Maternal nutrition affects immunity ‘programming' during the period of pre-natal and post-natal life. Over the last decade, epidemiological and experimental studies have helped to expedite more understanding of immunity ‘programming.' External exposures such as smoking, alcohol and drugs during fetal life have also shown to have an impact on immunity ‘programming.' In this review, the relationship between fetal programming and the immune system, such as effects on the various immune-cellular components through some evidence from epidemiological and experimental models will be discussed.

scholarly journals P2X7 Receptor–Mediated Inflammation in Cardiovascular Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Junteng Zhou ◽  
Zhichao Zhou ◽  
Xiaojing Liu ◽  
Hai-Yan Yin ◽  
Yong Tang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
P2x7 Receptor ◽  
Cardiac Fibrosis ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Experimental Studies ◽  
Therapeutic Interventions ◽  
Receptor Protein ◽  
Inflammasome Activation

Purinergic P2X7 receptor, a nonselective cation channel, is highly expressed in immune cells as well as cardiac smooth muscle cells and endothelial cells. Its activation exhibits to mediate nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activation, resulting in the release of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), and pyroptosis, thus triggering inflammatory response. These pathological mechanisms lead to the deterioration of various cardiovascular diseases, including atherosclerosis, arrhythmia, myocardial infarction, pulmonary vascular remodeling, and cardiac fibrosis. All these worsening cardiac phenotypes are proven to be attenuated after the P2X7 receptor inhibition in experimental studies. The present review aimed to summarize key aspects of P2X7 receptor–mediated inflammation and pyroptosis in cardiovascular diseases. The main focus is on the evidence addressing the involvement of the P2X7 receptor in the inflammatory responses to the occurrence and development of cardiovascular disease and therapeutic interventions.

scholarly journals Estrogen Receptor and Vascular Aging

2021 ◽  
Vol 2 ◽  
Author(s):  
Morgane Davezac ◽  
Melissa Buscato ◽  
Rana Zahreddine ◽  
Patrick Lacolley ◽  
Daniel Henrion ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cardiovascular Diseases ◽  
Experimental Studies ◽  
Hormonal Treatment ◽  
Protective Effects ◽  
Age Related ◽  
Nuclear Receptor Family ◽  
The Impact ◽  
Receptor Family

Cardiovascular diseases remain an age-related pathology in both men and women. These pathologies are 3-fold more frequent in men than in women before menopause, although this difference progressively decreases after menopause. The vasculoprotective role of estrogens are well established before menopause, but the consequences of their abrupt decline on the cardiovascular risk at menopause remain debated. In this review, we will attempt to summarize the main clinical and experimental studies reporting the protective effects of estrogens against cardiovascular diseases, with a particular focus on atherosclerosis, and the impact of aging and estrogen deprivation on their endothelial actions. The arterial actions of estrogens, but also part of that of androgens through their aromatization into estrogens, are mediated by the estrogen receptor (ER)α and ERβ. ERs belong to the nuclear receptor family and act by transcriptional regulation in the nucleus, but also exert non-genomic/extranuclear actions. Beside the decline of estrogens at menopause, abnormalities in the expression and/or function of ERs in the tissues, and particularly in arteries, could contribute to the failure of classic estrogens to protect arteries during aging. Finally, we will discuss how recent insights in the mechanisms of action of ERα could contribute to optimize the hormonal treatment of the menopause.

scholarly journals Biological activity and mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulphated derivatives

2016 ◽  
Vol 62 (1) ◽  
pp. 22-30 ◽  
Author(s):  
A.M. Popov ◽  
O.N. Krivoshapko ◽  
A.A. Klimovich ◽  
A.A. Artyukov
Keyword(s):  
Type 2 Diabetes ◽  
Biological Activity ◽  
Lipid Metabolism ◽  
Phenolic Compounds ◽  
Rosmarinic Acid ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Therapeutic Action ◽  
Carbohydrate And Lipid Metabolism

The review considers recent experimental studies of biological activity and mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulfated derivatives in diseases associated with disorders of carbohydrate and lipid metabolism. Particular attention is focused on the results of studies showing a high therapeutic potential of these phenolic compounds in their prophylactic and therapeutic use at experimental modeling of type 2 diabetes and hyperlipidemia. Based on the analysis of our results and the literature data putative mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulfated derivatives have been proposed.

Study of toxicity and peculiarities of biological effects of nanocomposite pectin-Ag: results of a subchronic experiment

2021 ◽  
Vol 29 (5) ◽  
pp. 25-33
Author(s):  
Vadzim Michailovich Vasilkevich ◽  
Ruslan Valerievich Bogdanov ◽  
Ksenia Sergeevna Gilevskaya ◽  
Victoria Igorevna Kulikouskaya
Keyword(s):  
Biological Effects ◽  
Experimental Studies ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Pectin Content ◽  
Target Organs ◽  
Toxicological Studies ◽  
Threshold Doses ◽  
20 Nm ◽  
Dose Dependent

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields. Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20-30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed. Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase. Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.

Perinatal exposure to Bisphenol A and developmental programming of the cardiovascular changes in the offspring

2021 ◽  
Vol 28 ◽  
Author(s):  
Srinivasa Rao Sirasanagandla ◽  
Isehaq Al-Huseini ◽  
R G Sumesh Sofin ◽  
Srijit Das
Keyword(s):  
Cardiovascular Diseases ◽  
Bisphenol A ◽  
Muscle Development ◽  
Experimental Studies ◽  
Positive Association ◽  
Developmental Programming ◽  
Present Review ◽  
Perinatal Exposure ◽  
Autonomic Tone ◽  
Mitochondrial Energy Metabolism

: Bisphenol A (BPA) is an industrial ubiquitous compound, frequently used to produce synthetic polymers and epoxy resins. BPA is a well-recognized endocrine disruptor and xenoestrogen compound. Evidence from epidemiological and experimental studies suggests that perinatal BPA exposure (gestation and/or lactation) increases the risk of developing various diseases, including the cardiovascular system. Developmental programming refers to environmental insults during the critical window of development that affect the structure and physiology of body systems, causing permanent changes in later stages. BPA influences the developmental programming of non-communicable diseases in the offspring. In the present review, we discuss the developmental programming of cardiovascular diseases related to perinatal exposure to BPA, supported by epidemiological and experimental evidence from published literature. The majority of the reported studies found a positive association between perinatal BPA exposure and adverse cardiovascular repercussions in the fetal, neonatal, and adulthood stages. The possible underlying mechanisms include epigenetic modifications of genes involved in cardiac muscle development, autonomic tone, collagenous and non-collagenous extracellular matrix, cardiac remodeling and calcium homeostasis, and mitochondrial energy metabolism. Epigenetics can modify the outcome of any disease. Hence, in the present review, we also discuss the role of epigenetics in preventing cardiovascular diseases following perinatal exposure to BPA. We also highlight how future treatment and drug delivery related to cardiovascular involvement could be based on epigenetic markers.

Developmental origins of health and disease

2018 ◽  
pp. 36-39
Author(s):  
Caroline Fall ◽  
Kalyanaraman Kumaran
Keyword(s):  
Early Life ◽  
Infant Development ◽  
Animal Experiments ◽  
Environmental Pollutants ◽  
Adult Life ◽  
Maternal Diabetes ◽  
Observational Research ◽  
Increased Risk ◽  
Health And Disease ◽  
And Function

Sub-optimal nutrition during foetal and infant development is associated with an increased risk of non-communicable diseases (NCDs) in adult life. Animal experiments show that this results from permanent effects on the structure and function of tissues and hormone systems (‘metabolic programming’), probably mediated by epigenetic changes. NCD risk is increased further by adiposity and/or unhealthy lifestyles in childhood or adulthood. Apart from nutrition, other early life environmental influences can programme later disease, including foetal ‘over-nutrition’ (maternal diabetes or obesity) and exposure to maternal smoking, environmental pollutants, and pregnancy complications. The concept that improving the nutrition and health of mothers pre-conceptionally and during pregnancy could prevent common NCDs has huge public health implications. However, unlike the robust demonstration of programming in experimental animals, the evidence in humans rests mainly on observational research. Intervention studies are ongoing to strengthen the evidence and to identify ways to improve early development and prevent NCDs.

More purinergic receptors deserve attention as therapeutic targets for the treatment of cardiovascular disease

2020 ◽  
Vol 319 (4) ◽  
pp. H723-H729 ◽  
Author(s):  
Bernhard Wernly ◽  
Zhichao Zhou (周稚超)
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Purinergic Receptors ◽  
Treatment Options ◽  
Experimental Studies ◽  
Therapeutic Targets ◽  
Independent Effect ◽  
Coronary Syndrome ◽  
Future Drug ◽  
New Treatment

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension, and diabetes. PRs have been targeted for the treatment of several cardiovascular diseases in a clinical setting. The P2Y12R antagonists such as clopidogrel, ticagrelor, and others are the most successful class of purinergic drugs targeting platelets for the treatment of acute coronary syndrome. In addition to targeting platelets, ticagrelor may exert P2Y12R-independent effect by targeting erythrocyte-mediated purinergic activation. The partial A1R agonist neladenoson and the A2AR agonist regadenoson have been applied in cardiovascular medicine. In experimental studies, many other PRs have been shown to play a significant role in the development and progression of cardiovascular diseases, and targeting these receptors have resulted in promising outcomes. Therefore, many of these PRs including A2BR, A3R, P2X3R, P2X4R, P2X7R, P2Y1R, P2Y4R, P2Y6R, and P2Y11R can be considered as therapeutic targets. However, the multitude of PR subtypes expressed in different cells of the cardiovascular system may constitute a challenge whether single or multiple receptors should be targeted at the same time for the best efficacy. The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development.

scholarly journals Neurotrophins regulate cholinergic synaptic transmission in cultured rat sympathetic neurons through a p75-dependent mechanism

2013 ◽  
Vol 109 (2) ◽  
pp. 485-496 ◽  
Author(s):  
J. A. Luther ◽  
J. Enes ◽  
S. J. Birren
Keyword(s):  
Cardiovascular Diseases ◽  
Sympathetic Neurons ◽  
Second Messengers ◽  
Ceramide Synthase ◽  
Cholinergic Synaptic Transmission ◽  
Target Organs ◽  
Synthase Inhibitor ◽  
Neurotrophin Signaling ◽  
Dependent Mechanism

The sympathetic nervous system regulates many essential physiological systems, and its dysfunction is implicated in cardiovascular diseases. Mechanisms that control the strength of sympathetic output are therefore potential targets for the management of these disorders. Here we show that neurotrophins rapidly potentiate cholinergic transmission between cultured rat sympathetic neurons. We found that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), acting at the p75 receptor, increased the amplitude of excitatory postsynaptic currents (EPSCs). We observed increased amplitude but not frequency of miniature synaptic currents after p75 activation, suggesting that p75 acts postsynaptically to modulate transmission at these synapses. This neurotrophic modulation enhances cholinergic EPSCs via sphingolipid signaling. Application of sphingolactone-24, an inhibitor of neutral sphingomyelinase, blocked the effect of BDNF, implicating a sphingolipid pathway. Furthermore, application of the p75-associated sphingolipid second messengers C2-ceramide and d- erythro-sphingosine restricted to the postsynaptic cell mimicked BDNF application. Postsynaptic blockade of ceramide production with fumonisin, a ceramide synthase inhibitor, blocked the effects of BDNF and d- erythro-sphingosine, implicating ceramide or ceramide phosphate as the active signal. Together these data suggest that neurotrophin signaling, which occurs in vivo via release from sympathetic neurons and target tissues such as the heart, acutely regulates the strength of the sympathetic postganglionic response to central cholinergic inputs. This pathway provides a potential mechanism for modulating the strength of sympathetic drive to target organs such as the heart and could play a role in the development of cardiovascular diseases.

scholarly journals Utility of Circulating MicroRNAs as Clinical Biomarkers for Cardiovascular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Altaf A. Kondkar ◽  
Khaled K. Abu-Amero
Keyword(s):  
Cardiovascular Diseases ◽  
Noncoding Rna ◽  
Experimental Studies ◽  
Future Perspective ◽  
Mirna Biogenesis ◽  
Circulating Mirnas ◽  
Clinical Biomarkers ◽  
Diagnostic Potential ◽  
Gene And Protein Expression ◽  
Severity Prediction

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene and protein expression by translational repression and/or mRNA degradation. miRNAs are implicated in the pathogenesis of various cardiovascular diseases and have become potential targets for therapeutic intervention. Their stability and presence in variety of readily accessible cell types including whole blood, serum, plasma, and other body fluids render them as potential source of a clinical biomarker. This review provides a brief overview of miRNA biogenesis and function, the diagnostic potential of circulating extracellular miRNA and their specific role in vivo in various cardiovascular settings, and their future perspective as clinical biomarkers. It is clearly evident from experimental studies that miRNAs are responsible for the regulation of several biological functions and alterations in cardiovascular diseases. Current data supports the concept of using circulating miRNAs as a biomarker in cardiovascular disease. It remains to be seen, however, whether circulating miRNAs can fulfil this role to improve risk and severity prediction.

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