scholarly journals Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3795
Author(s):  
James N. Tsoporis ◽  
Ioannis-Alexandros Drosatos ◽  
Sahil Gupta ◽  
Hajera Amatullah ◽  
Shehla Izhar ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Original Data ◽  
Vascular Surgical Procedures ◽  
Gene Encoding ◽  
Future Studies ◽  
Cardiac Pathophysiology ◽  
Recessive Form ◽  
The Central Nervous System

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson’s disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1′s role as a plausible novel therapeutic target for cardiovascular disease.

scholarly journals NEUROPROTECTIVE ROLE OF ASCORBIC ACID: ANTIOXIDANT AND NON-ANTIOXIDANT FUNCTIONS

2018 ◽  
Vol 11 (10) ◽  
pp. 30 ◽  
Author(s):  
Arun Kumar ◽  
Reena V Saini ◽  
Adesh K Saini
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glutamate Toxicity ◽  
Cellular Functions ◽  
Dietary Antioxidant ◽  
The Central Nervous System

Ascorbic acid (AA) or Vitamin C is an important antioxidant which participates in numerous cellular functions. Although in human plasma its concentration is in micromolars but it reaches millimolar concentrations in most of the human tissues. The high ascorbate cellular concentrations are generated and maintained by a specific sodium-dependent Vitamin C transporter type 2 (SVCT2, member of Slc23 family). Metabolic processes recycle Vitamin C from its oxidized forms (ascorbate) inside the cells. AA concentration is highest in the neurons of the central nervous system (CNS) of mammals, and deletion of its transporter affects mice brain and overall survival. In the CNS, intracellular ascorbate serves several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. SVCT2 maintains neuronal ascorbate content in CNS which has relevance for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. As ascorbate supplements decrease infarct size in ischemia-reperfusion injury and protect neurons from oxidative damage, it is a vital dietary antioxidant. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis in CNS and the extent to which ascorbate affects brain function as an antioxidant.

scholarly journals The Role of Estrogen Receptors in Cardiovascular Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4314 ◽  
Author(s):  
Laila Aryan ◽  
David Younessi ◽  
Michael Zargari ◽  
Somanshu Banerjee ◽  
Jacqueline Agopian ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Estrogen Receptor ◽  
Ejection Fraction ◽  
Estrogen Receptors ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vascular Pathology ◽  
Reduced Ejection Fraction

Cardiovascular Diseases (CVDs) are the leading cause of death globally. More than 17 million people die worldwide from CVD per year. There is considerable evidence suggesting that estrogen modulates cardiovascular physiology and function in both health and disease, and that it could potentially serve as a cardioprotective agent. The effects of estrogen on cardiovascular function are mediated by nuclear and membrane estrogen receptors (ERs), including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G-protein-coupled ER (GPR30 or GPER). Receptor binding in turn confers pleiotropic effects through both genomic and non-genomic signaling to maintain cardiovascular homeostasis. Each ER has been implicated in multiple pre-clinical cardiovascular disease models. This review will discuss current reports on the underlying molecular mechanisms of the ERs in regulating vascular pathology, with a special emphasis on hypertension, pulmonary hypertension, and atherosclerosis, as well as in regulating cardiac pathology, with a particular emphasis on ischemia/reperfusion injury, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction.

scholarly journals Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease

2013 ◽  
Vol 304 (4) ◽  
pp. H491-H500 ◽  
Author(s):  
Peter A. Hecker ◽  
Jane A. Leopold ◽  
Sachin A. Gupte ◽  
Fabio A. Recchia ◽  
William C. Stanley
Keyword(s):  
Cardiovascular Disease ◽  
G6pd Deficiency ◽  
Cholesterol Synthesis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pressure Overload ◽  
Protective Role ◽  
Pentose Phosphate ◽  
Protective Effects ◽  
Glucose 6 Phosphate Dehydrogenase

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-determining step in the pentose phosphate pathway and produces NADPH to fuel glutathione recycling. G6PD deficiency is the most common enzyme deficiency in humans and affects over 400 million people worldwide; however, its impact on cardiovascular disease is poorly understood. The glutathione pathway is paramount to antioxidant defense, and G6PD-deficient cells do not cope well with oxidative damage. Limited clinical evidence indicates that G6PD deficiency may be associated with hypertension. However, there are also data to support a protective role of G6PD deficiency in decreasing the risk of heart disease and cardiovascular-associated deaths, perhaps through a decrease in cholesterol synthesis. Studies in G6PD-deficient (G6PDX) mice are mixed and provide evidence for both protective and deleterious effects. G6PD deficiency may provide a protective effect through decreasing cholesterol synthesis, superoxide production, and reductive stress. However, recent studies indicate that G6PDX mice are moderately more susceptible to ventricular dilation in response to myocardial infarction or pressure overload-induced heart failure. Furthermore, G6PDX hearts do not recover as well as nondeficient mice when faced with ischemia-reperfusion injury, and G6PDX mice are susceptible to the development of age-associated cardiac hypertrophy. Overall, the limited available data indicate a complex interplay in which adverse effects of G6PD deficiency may outweigh potential protective effects in the face of cardiac stress. Definitive clinical studies in large populations are needed to determine the effects of G6PD deficiency on the development of cardiovascular disease and subsequent outcomes.

scholarly journals A review of the relationship between long noncoding RNA and post-stroke injury repair

2019 ◽  
Vol 47 (10) ◽  
pp. 4619-4624
Author(s):  
Yao Wang ◽  
Wei-Yi Pan ◽  
Jun-Sheng Ge ◽  
Xiao-Dong Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Noncoding Rna ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Regulatory Sequences ◽  
Post Injury ◽  
Injury Repair ◽  
Post Stroke ◽  
The Central Nervous System

Stroke is a cerebrovascular circulation disorder with sudden onset, which causes disorder of ion balance, inflammation, and acidosis, and that in turn induces ischemia-reperfusion injury, influencing the prognosis of stroke patients. Long noncoding RNAs (lncRNAs) are regulatory sequences involved at the transcriptional, post-transcriptional, and epigenetic levels, have high specific expression in the central nervous system, and effectively regulate the development of the central nervous system and progression of diseases. Stroke induces changes in the expression of many lncRNAs. Therefore, lncRNAs play an important role in the complex pathological process of stroke. Exploring lncRNA could facilitate a comprehensive understanding of the pathological mechanism of stroke and the post-injury molecular regulatory network. However, there are few reports on the role of lncRNA in the pathological development of stroke. In the present review, we discuss the association of lncRNA with post-stroke injury repair.

scholarly journals The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Chaoran Chen ◽  
Xiang Zhou ◽  
Jialiang He ◽  
Zhenxing Xie ◽  
Shufang Xia ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vital Role ◽  
Pathological Process ◽  
Peripheral Organs ◽  
Multiple Organs ◽  
Long Time ◽  
The Central Nervous System

Ischemia-reperfusion (I/R) injury is a common pathological process, which may lead to dysfunctions and failures of multiple organs. A flawless medical way of endogenous therapeutic target can illuminate accurate clinical applications. γ-Aminobutyric acid (GABA) has been known as a marker in I/R injury of the central nervous system (mainly in the brain) for a long time, and it may play a vital role in the occurrence of I/R injury. It has been observed that throughout cerebral I/R, levels, syntheses, releases, metabolisms, receptors, and transmissions of GABA undergo complex pathological variations. Scientists have investigated the GABAergic enhancers for attenuating cerebral I/R injury; however, discussions on existing problems and mechanisms of available drugs were seldom carried out so far. Therefore, this review would summarize the process of pathological variations in the GABA system under cerebral I/R injury and will cover corresponding probable issues and mechanisms in using GABA-related drugs to illuminate the concern about clinical illness for accurately preventing cerebral I/R injury. In addition, the study will summarize the increasing GABA signals that can prevent I/R injuries occurring in peripheral organs, and the roles of GABA were also discussed correspondingly.

scholarly journals Oxidative Stress as a Mediator of Cardiovascular Disease

2009 ◽  
Vol 2 (5) ◽  
pp. 259-269 ◽  
Author(s):  
Maqsood M. Elahi ◽  
Yu Xiang Kong ◽  
Bashir M. Matata
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion Injury ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Redox Balance ◽  
Reactive Oxidant Species ◽  
Reactive Oxidant

During physiological processes molecules undergo chemical changes involving reducing and oxidizing reactions. A molecule with an unpaired electron can combine with a molecule capable of donating an electron. The donation of an electron is termed as oxidation whereas the gaining of an electron is called reduction. Reduction and oxidation can render the reduced molecule unstable and make it free to react with other molecules to cause damage to cellular and sub-cellular components such as membranes, proteins and DNA. In this paper, we have discussed the formation of reactive oxidant species originating from a variety of sources such as nitric oxide (NO) synthase (NOS), xanthine oxidases (XO), the cyclooxygenases, nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase isoforms and metal-catalyzed reactions. In addition, we present a treatise on the physiological defences such as specialized enzymes and antioxidants that maintain reduction-oxidation (redox) balance. We have also given an account of how enzymes and antioxidants can be exhausted by the excessive production of reactive oxidant species (ROS) resulting in oxidative stress/nitrosative stress, a process that is an important mediator of cell damage. Important aspects of redox imbalance that triggers the activity of a number of signaling pathways including transcription factors activity, a process that is ubiquitous in cardiovascular disease related to ischemia/reperfusion injury have also been presented.

scholarly journals Recognition Functions of Pentameric C-Reactive Protein in Cardiovascular Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Alok Agrawal ◽  
Toh B. Gang ◽  
Antonio E. Rusiñol
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Complement Activation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Host Cells ◽  
Ldl Oxidation ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Binding Function

C-reactive protein (CRP) performs two recognition functions that are relevant to cardiovascular disease. First, in its native pentameric conformation, CRP recognizes molecules and cells with exposed phosphocholine (PCh) groups, such as microbial pathogens and damaged cells. PCh-containing ligand-bound CRP activates the complement system to destroy the ligand. Thus, the PCh-binding function of CRP is defensive if it occurs on foreign pathogens because it results in the killing of the pathogen via complement activation. On the other hand, the PCh-binding function of CRP is detrimental if it occurs on injured host cells because it causes more damage to the tissue via complement activation; this is how CRP worsens acute myocardial infarction and ischemia/reperfusion injury. Second, in its nonnative pentameric conformation, CRP also recognizes atherogenic low-density lipoprotein (LDL). Recent data suggest that the LDL-binding function of CRP is beneficial because it prevents formation of macrophage foam cells, attenuates inflammatory effects of LDL, inhibits LDL oxidation, and reduces proatherogenic effects of macrophages, raising the possibility that nonnative CRP may show atheroprotective effects in experimental animals. In conclusion, temporarily inhibiting the PCh-binding function of CRP along with facilitating localized presence of nonnative pentameric CRP could be a promising approach to treat atherosclerosis and myocardial infarction. There is no need to stop the biosynthesis of CRP.

scholarly journals Polymers and Nanoparticles for Statin Delivery: Current Use and Future Perspectives in Cardiovascular Disease

Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 711
Author(s):  
Antonio Nenna ◽  
Francesco Nappi ◽  
Domenico Larobina ◽  
Emanuele Verghi ◽  
Massimo Chello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Specific Interaction ◽  
Cardiac Regeneration ◽  
Statin Treatment ◽  
Current Evidence ◽  
Vascular Endothelial ◽  
Mortality And Morbidity ◽  
Artery Disease

Atherosclerosis-related coronary artery disease (CAD) is one of the leading sources of mortality and morbidity in the world. Primary and secondary prevention appear crucial to reduce CAD-related complications. In this scenario, statin treatment was shown to be clinically effective in the reduction of adverse events, but systemic administration provides suboptimal results. As an attempt to improve bioavailability and effectiveness, polymers and nanoparticles for statin delivery were recently investigated. Polymers and nanoparticles can help statin delivery and their effects by increasing oral bioavailability or enhancing target-specific interaction, leading to reduced vascular endothelial dysfunction, reduced intimal hyperplasia, reduced ischemia-reperfusion injury, increased cardiac regeneration, positive remodeling in the extracellular matrix, reduced neointimal growth and increased re-endothelization. Moreover, some innovative aspects described in other cardiovascular fields could be translated into the CAD scenario. Recent preclinical studies are underlining the effect of statins in the stimulation and differentiation of endogenous cardiac stem cells, as well as in targeting of local adverse conditions implicated in atherosclerosis, and statin delivery through poly-lactic-co-glycolic acid (PLGA) appears the most promising aspect of current research to enhance drug activity. The present review intends to summarize the current evidence about polymers and nanoparticles for statin delivery in the field of cardiovascular disease, trying to shed light on this topic and identify new avenues for future studies.

Cardioprotective Function of Green Rooibos (Aspalathus linearis) Extract Supplementation in Ex Vivo Ischemic Prediabetic Rat Hearts

Planta Medica ◽  
2020 ◽  
Author(s):  
Sybrand Engelbrecht Smit ◽  
Claudine Manirafasha ◽  
Erna Marais ◽  
Rabia Johnson ◽  
Barbara Huisamen
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Insulin Independence ◽  
Rat Hearts ◽  
Insulin Dependence ◽  
High Caloric Diet

AbstractDiabetic patients develop ischemic heart disease and strokes more readily. Following an ischemic event, restoration of blood flow increases oxidative stress resulting in myocardial damage, termed ischemia/reperfusion injury. Aspalathus linearis (rooibos), rich in the antioxidant phenolic compound aspalathin, has been implicated as cardioprotective against ischemia/reperfusion injury with undefined mechanism in control rats. Primarily, the therapeutic potential of Afriplex green rooibos extract to prevent ischemia/reperfusion injury in cardiovascular disease-compromised rats was investigated. Additionally, Afriplex Green rooibos extractʼs cardioprotective signaling on metabolic markers and stress markers was determined using western blotting. Three hundred male Wistar rats received either 16-wk standard diet or high-caloric diet. During the final 6 wk, half received 60 mg/kg/day Afriplex green rooibos extract, containing 12.48% aspalathin. High-caloric diet increased body weight, body fat, fasting serum triglycerides, and homeostatic model assessment of insulin resistance – indicative of prediabetes. High-caloric diet rats had increased heart mass, infarct size, and decreased heart function. Afriplex green rooibos extract treatment for 6 wk lowered pre-ischemic heart rate, reduced infarct size, and improved heart function pre- and post-ischemia, without significantly affecting biometric parameters. Stabilized high-caloric diet hearts had decreased insulin independence via adenosine monophosphate activated kinase and increased inflammation (p38 mitogen-activated protein kinase), whereas Afriplex green rooibos extract treatment decreased insulin dependence (protein kinase B) and conferred anti-inflammatory effect. After 20 min ischemia, high-caloric diet hearts had upregulated ataxia–telangiectasia mutated kinase decreased insulin independence, and downregulated insulin dependence and glycogen synthase kinase 3 β inhibition. In contrast, Afriplex green rooibos extract supplementation downregulated insulin independence and inhibited extracellular signal-regulated kinase 1 and 2. During reperfusion, all protective signaling was decreased in high-caloric diet, while Afriplex green rooibos extract supplementation reduced oxidative stress (c-Jun N-terminal kinases 1 and 2) and inflammation. Taken together, Afriplex green rooibos extract supplementation for 6 wk preconditioned cardiovascular disease-compromised rat hearts against ischemia/reperfusion injury by lowering inflammation, oxidative stress, and heart rate.

scholarly journals Emerging role of VCP/p97 in cardiovascular diseases: novel insights and therapeutic opportunities

2021 ◽  
Author(s):  
Hongyang Shu ◽  
Yizhong Peng ◽  
Weijian Hang ◽  
Ning Zhou ◽  
Dao Wen Wang
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Reperfusion Injury ◽  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Heart Research

Valosin-containing protein (VCP/p97) is a member of the conserved type II AAA+ (ATPases associated with diverse cellular activities) family of proteins with multiple biological functions, especially in protein homeostasis. Mutations in VCP/p97 are reportedly related to unique autosomal dominant diseases, which may worsen cardiac function. Although the structure of VCP/p97 has been clearly characterized, with reports of high abundance in the heart, research focusing on the molecular mechanisms underpinning the roles of VCP/p97 in the cardiovascular system has been recently undertaken over the past decades. Recent studies have shown that VCP/p97 deficiency affects myocardial fibers and induces heart failure, while overexpression of VCP/p97 eliminates ischemia/reperfusion injury and relieves pathological cardiac hypertrophy caused by cardiac pressure overload, which is related to changes in the mitochondria and calcium overload. However, certain studies have drawn opposing conclusions, including the mitigation of ischemia/reperfusion injury via inhibition of VCP/p97 ATPase activity. Nevertheless, these emerging studies shed light on the role of VCP/p97 and its therapeutic potential in cardiovascular diseases. In other words, VCP/p97 may be involved in the development of cardiovascular disease, and is anticipated to be a new therapeutic target. This review summarizes current findings regarding VCP/p97 in the cardiovascular system for the first time, and discusses the role of VCP/p97 in cardiovascular disease.

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