scholarly journals Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea

2018 ◽  
Vol 315 (3) ◽  
pp. H429-H447 ◽  
Author(s):  
Andrew C. Bulmer ◽  
Bhavisha Bakrania ◽  
Eugene F. Du Toit ◽  
Ai-Ching Boon ◽  
Paul J. Clark ◽  
...  
Keyword(s):  
Clinical Medicine ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Chronic Obstructive ◽  
Protective Properties ◽  
Physiological Importance ◽  
Bilirubin Excretion ◽  
Chronic Obstructive Pulmonary Diseases ◽  
Atherosclerotic Process

Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert’s syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.

scholarly journals MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

2020 ◽  
Vol 21 (12) ◽  
pp. 4370
Author(s):  
Montserrat Climent ◽  
Giacomo Viggiani ◽  
Ya-Wen Chen ◽  
Gerald Coulis ◽  
Alessandra Castaldi
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Redox Balance ◽  
Chronic Obstructive ◽  
Transcriptional Level ◽  
Control Mechanisms ◽  
Redox Equilibrium ◽  
Obstructive Pulmonary Disease

Reactive oxygen species (ROS) affect many cellular functions and the proper redox balance between ROS and antioxidants contributes substantially to the physiological welfare of the cell. During pathological conditions, an altered redox equilibrium leads to increased production of ROS that in turn may cause oxidative damage. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level contributing to all major cellular processes, including oxidative stress and cell death. Several miRNAs are expressed in response to ROS to mediate oxidative stress. Conversely, oxidative stress may lead to the upregulation of miRNAs that control mechanisms to buffer the damage induced by ROS. This review focuses on the complex crosstalk between miRNAs and ROS in diseases of the cardiac (i.e., cardiac hypertrophy, heart failure, myocardial infarction, ischemia/reperfusion injury, diabetic cardiomyopathy) and pulmonary (i.e., idiopathic pulmonary fibrosis, acute lung injury/acute respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, lung cancer) compartments. Of note, miR-34a, miR-144, miR-421, miR-129, miR-181c, miR-16, miR-31, miR-155, miR-21, and miR-1/206 were found to play a role during oxidative stress in both heart and lung pathologies. This review comprehensively summarizes current knowledge in the field.

scholarly journals Carnitine Palmitoyltransferase System: A New Target for Anti-Inflammatory and Anticancer Therapy?

2021 ◽  
Vol 12 ◽  
Author(s):  
Muyun Wang ◽  
Kun Wang ◽  
Ximing Liao ◽  
Haiyang Hu ◽  
Liangzhi Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Chronic Obstructive ◽  
Hepatic Ischemia ◽  
Kidney Fibrosis ◽  
Nonalcoholic Fatty Liver ◽  
Anti Inflammatory

Lipid metabolism involves multiple biological processes. As one of the most important lipid metabolic pathways, fatty acid oxidation (FAO) and its key rate-limiting enzyme, the carnitine palmitoyltransferase (CPT) system, regulate host immune responses and thus are of great clinical significance. The effect of the CPT system on different tissues or organs is complex: the deficiency or over-activation of CPT disrupts the immune homeostasis by causing energy metabolism disorder and inflammatory oxidative damage and therefore contributes to the development of various acute and chronic inflammatory disorders and cancer. Accordingly, agonists or antagonists targeting the CPT system may become novel approaches for the treatment of diseases. In this review, we first briefly describe the structure, distribution, and physiological action of the CPT system. We then summarize the pathophysiological role of the CPT system in chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, chronic granulomatous disease, nonalcoholic fatty liver disease, hepatic ischemia–reperfusion injury, kidney fibrosis, acute kidney injury, cardiovascular disorders, and cancer. We are also concerned with the current knowledge in either preclinical or clinical studies of various CPT activators/inhibitors for the management of diseases. These compounds range from traditional Chinese medicines to novel nanodevices. Although great efforts have been made in studying the different kinds of CPT agonists/antagonists, only a few pharmaceuticals have been applied for clinical uses. Nevertheless, research on CPT activation or inhibition highlights the pharmacological modulation of CPT-dependent FAO, especially on different CPT isoforms, as a promising anti-inflammatory/antitumor therapeutic strategy for numerous disorders.

scholarly journals What we need to know about lipid-associated injury in case of renal ischemia-reperfusion

2018 ◽  
Vol 315 (6) ◽  
pp. F1714-F1719 ◽  
Author(s):  
Pauline Erpicum ◽  
Pascal Rowart ◽  
Jean-Olivier Defraigne ◽  
Jean-Marie Krzesinski ◽  
François Jouret
Keyword(s):  
Energy Demand ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Cell Functions ◽  
Associated Injury ◽  
Cortex Area

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch toward anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting in a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

scholarly journals MicroRNA-26a: An Emerging Regulator of Renal Biology and Disease

2019 ◽  
Vol 44 (3) ◽  
pp. 287-297 ◽  
Author(s):  
Xiaoyan Li ◽  
Xiao Pan ◽  
Xianghui Fu ◽  
Yi Yang ◽  
Jianghua Chen ◽  
...  
Keyword(s):  
Target Genes ◽  
Mesangial Cells ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Autoimmune Diabetes ◽  
Ischemia Reperfusion ◽  
Biological Processes ◽  
Immune Attack ◽  
Renal System ◽  
And Function

MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that modulate many key biological processes by simultaneously suppressing multiple target genes. Among them, miR-26a, a conserved miRNA among vertebrates, is highly expressed in various tissues. Accumulating evidence demonstrates that miR-26a plays pivotal roles in cellular differentiation, cell growth, apoptosis, and metastasis, thereby participating in the initiation and development of various human diseases, such as metabolic disease and cancer. More recently, miR-26a was found as a versatile regulator of renal biology and disease. miR-26a is intensively involved in the maintenance of podocyte homeostasis and the actin cytoskeleton. It is also able to modulate the homeostasis and function of mesangial cells. In addition, miR-26a affects the expansion of regulatory T cells in the context of ischemia-reperfusion injury and autoimmune diabetes and thus protects the renal system from immune attack. These available data strongly suggest that renal miR-26a possesses critical pathological functions and represents a potential target for renal disease therapies. This review summarizes current knowledge of miR-26a in renal biology and disease, laying the foundation for exploring its previously unknown functions and mechanisms in the renal system.

scholarly journals ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia/Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Letteria Minutoli ◽  
Domenico Puzzolo ◽  
Mariagrazia Rinaldi ◽  
Natasha Irrera ◽  
Herbert Marini ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Ion Homeostasis ◽  
Inflammasome Activation ◽  
Mortality And Morbidity ◽  
Arterial Blood ◽  
Nlrp3 Inflammasome Activation

Ischemia and reperfusion (I/R) causes a reduction in arterial blood supply to tissues, followed by the restoration of perfusion and consequent reoxygenation. The reestablishment of blood flow triggers further damage to the ischemic tissue through reactive oxygen species (ROS) accumulation, interference with cellular ion homeostasis, and inflammatory responses to cell death. In normal conditions, ROS mediate important beneficial responses. When their production is prolonged or elevated, harmful events are observed with peculiar cellular changes. In particular, during I/R, ROS stimulate tissue inflammation and induce NLRP3 inflammasome activation. The mechanisms underlying the activation of NLRP3 are several and not completely elucidated. It was recently shown that NLRP3 might sense directly the presence of ROS produced by normal or malfunctioning mitochondria or indirectly by other activators of NLRP3. Aim of the present review is to describe the current knowledge on the role of NLRP3 in some organs (brain, heart, kidney, and testis) after I/R injury, with particular regard to the role played by ROS in its activation. Furthermore, as no specific therapy for the prevention or treatment of the high mortality and morbidity associated with I/R is available, the state of the art of the development of novel therapeutic approaches is illustrated.

Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning

2003 ◽  
Vol 284 (1) ◽  
pp. G15-G26 ◽  
Author(s):  
Hartmut Jaeschke
Keyword(s):  
Reperfusion Injury ◽  
Liver Surgery ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
Cellular Mechanisms ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and reperfusion.

scholarly journals Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 974 ◽  
Author(s):  
Aileen Hill ◽  
Sebastian Wendt ◽  
Carina Benstoem ◽  
Christina Neubauer ◽  
Patrick Meybohm ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Vitamin C ◽  
Acute Stress ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Organ Damage ◽  
Current Evidence ◽  
Organ Systems

The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C’s effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

scholarly journals Binding Features and Functions of ATG3

2021 ◽  
Vol 9 ◽  
Author(s):  
Dongmei Fang ◽  
Huazhong Xie ◽  
Tao Hu ◽  
Hao Shan ◽  
Min Li
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Cellular Tissue ◽  
Dependent Manner ◽  
Conjugation System ◽  
Autophagosome Formation ◽  
Binding Partners ◽  
Independent Functions ◽  
Evolutionarily Conserved

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related (ATG) genes are indispensable for autophagosome formation. ATG3 is one of the key genes involved in autophagy, and its homologs are common in eukaryotes. During autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, contributing to phagophore elongation. ATG3 has also been found to participate in many physiological and pathological processes in an autophagy-dependent manner, such as tumor occurrence and progression, ischemia–reperfusion injury, clearance of pathogens, and maintenance of organelle homeostasis. Intriguingly, a few studies have recently discovered the autophagy-independent functions of ATG3, including cell differentiation and mitosis. Here, we summarize the current knowledge of ATG3 in autophagosome formation, highlight its binding partners and binding sites, review its autophagy-dependent functions, and provide a brief introduction into its autophagy-independent functions.

scholarly journals Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jakub Szyller ◽  
Iwona Bil-Lula
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Physical Exercises ◽  
Shock Proteins

Heat shock proteins (HSPs) are molecular chaperones produced in response to oxidative stress (OS). These proteins are involved in the folding of newly synthesized proteins and refolding of damaged or misfolded proteins. Recent studies have been focused on the regulatory role of HSPs in OS and ischemia/reperfusion injury (I/R) where reactive oxygen species (ROS) play a major role. ROS perform many functions, including cell signaling. Unfortunately, they are also the cause of pathological processes leading to various diseases. Biological pathways such as p38 MAPK, HSP70 and Akt/GSK-3β/eNOS, HSP70, JAK2/STAT3 or PI3K/Akt/HSP70, and HSF1/Nrf2-Keap1 are considered in the relationship between HSP and OS. New pathophysiological mechanisms involving ROS are being discovered and described the protein network of HSP interactions. Understanding of the mechanisms involved, e.g., in I/R, is important to the development of treatment methods. HSPs are multifunctional proteins because they closely interact with the antioxidant and the nitric oxide generation systems, such as HSP70/HSP90/NOS. A deficiency or excess of antioxidants modulates the activation of HSF and subsequent HSP biosynthesis. It is well known that HSPs are involved in the regulation of several redox processes and play an important role in protein-protein interactions. The latest research focuses on determining the role of HSPs in OS, their antioxidant activity, and the possibility of using HSPs in the treatment of I/R consequences. Physical exercises are important in patients with cardiovascular diseases, as they affect the expression of HSPs and the development of OS.

scholarly journals The Emerging Role of Irisin in Cardiovascular Diseases

2021 ◽  
Author(s):  
Jinjuan Fu ◽  
Fangtang Li ◽  
Yuanjuan Tang ◽  
Lin Cai ◽  
Chunyu Zeng ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Fibronectin Type Iii ◽  
Artery Disease ◽  
Myocardial Ischemia Reperfusion ◽  
Membrane Spanning ◽  
Fibronectin Type Iii Domain ◽  
Insulin Use

Abstract Irisin, a novel hormone like polypeptide, is cleaved and secreted by an unknown protease from a membrane‐spanning protein, FNDC5 (fibronectin type III domain‐containing protein 5). The current knowledge on the biological functions of irisin includes browning white adipose tissue, regulating insulin use, and anti‐inflammatory and antioxidative properties. Dysfunction of irisin has shown to be involved in cardiovascular diseases such as hypertension, coronary artery disease, myocardial infarction, and myocardial ischemia–reperfusion injury. Moreover, irisin gene variants are also associated with cardiovascular diseases. In this review, we discuss the current knowledge on irisin‐mediated regulatory mechanisms and their roles in the pathogenesis of cardiovascular diseases.

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