Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications

2009 ◽  
Vol 117 (3) ◽  
pp. 95-109 ◽  
Author(s):  
Jianli Niu ◽  
Pappachan E. Kolattukudy
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Zinc Finger Protein ◽  
Plaque Rupture ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Protective Effects ◽  
Ischaemia Reperfusion Injury

Many of the major diseases, including cardiovascular disease, are widely recognized as inflammatory diseases. MCP-1 (monocyte chemotactic protein-1) plays a critical role in the development of cardiovascular diseases. MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the subendothelial space where they become foam cells, initiating fatty streak formation that leads to atherosclerotic plaque formation. Inflammatory macrophages probably play a role in plaque rupture and the resulting ischaemic episode as well as restenosis after angioplasty. There is strong evidence that MCP-1 plays a major role in myocarditis, ischaemia/reperfusion injury in the heart and in transplant rejection. MCP-1 also plays a role in cardiac repair and manifests protective effects under certain conditions. Such protective effects may be due to the induction of protective ER (endoplasmic reticulum) stress chaperones by MCP-1. Under sustained ER stress caused by chronic exposure to MCP-1, the protection would break down resulting in the development of heart failure. MCP-1 is also involved in ischaemic angiogenesis. The recent advances in our understanding of the molecular mechanisms that might be involved in the roles that MCP-1 plays in cardiovascular disease are reviewed. The gene expression changes induced by the signalling events triggered by MCP-1 binding to its receptor include the induction of a novel zinc-finger protein called MCPIP (MCP-1-induced protein), which plays critical roles in the development of the pathophysiology caused by MCP-1 production. The role of the MCP-1/CCR2 (CC chemokine receptor 2) system in diabetes, which is a major risk factor for cardiovascular diseases, is also reviewed briefly. MCP-1/CCR2- and/or MCPIP-targeted therapeutic approaches to intervene in inflammatory diseases, including cardiovascular diseases, may be feasible.

scholarly journals The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2194
Author(s):  
Yi-Zhen Wang ◽  
Ebenezeri Erasto Ngowi ◽  
Di Wang ◽  
Hui-Wen Qi ◽  
Mi-Rong Jing ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Cell Types ◽  
Special Focus ◽  
Protective Effects ◽  
Improve Heart Function ◽  
Different Cell Types

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

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.

Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease

2021 ◽  
Author(s):  
Haleh Vaez ◽  
Hamid Soraya ◽  
Alireza Garjani ◽  
Tooba Gholikhani
Keyword(s):  
Cardiovascular Diseases ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Adenosine Monophosphate ◽  
Ampk Signaling ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Energy Sensor

Toll-like receptors (TLRs) are essential receptors of the innate immune system, playing a significant role in cardiovascular diseases. TLR4, with the highest expression among TLRs in the heart, has been investigated extensively for its critical role in different myocardial inflammatory conditions. Studies suggest that inhibition of TLR4 signaling pathways reduces inflammatory responses and even prevents additional injuries to the already damaged myocardium. Recent research results have led to a hypothesis that there may be a relation between TLR4 expression and 5' adenosine monophosphate-activated protein kinase (AMPK) signaling in various inflammatory conditions, including cardiovascular diseases. AMPK, as a cellular energy sensor, has been reported to show anti-inflammatory effects in various models of inflammatory diseases. AMPK, in addition to its physiological acts in the heart, plays an essential role in myocardial ischemia and hypoxia by activating various energy production pathways. Herein we will discuss the role of TLR4 and AMPK in cardiovascular diseases and a possible relation between TLRs and AMPK as a novel therapeutic target. In our opinion, AMPK-related TLR modulators will find application in treating different immune-mediated inflammatory disorders, especially inflammatory cardiac diseases, and present an option that will be widely used in clinical practice in the future.

Pathophysiological relevance of macrophage subsets in atherogenesis

2017 ◽  
Vol 117 (01) ◽  
pp. 07-18 ◽  
Author(s):  
Luca Liberale ◽  
Franco Dallegri ◽  
Federico Carbone ◽  
Fabrizio Montecucco
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Plaque Rupture ◽  
Current Knowledge ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Multiple Phenotypes ◽  
Adenosine Receptor Agonist ◽  
Macrophage Subsets

SummaryMacrophages are highly heterogeneous and plastic cells. They were shown to play a critical role in all stages of atherogenesis, from the initiation to the necrotic core formation and plaque rupture. Lesional macrophages primarily derive from blood monocyte, but local macrophage proliferation as well as differentiation from smooth muscle cells have also been described. Within atherosclerotic plaques, macrophages rapidly respond to changes in the microenvironment, shifting between pro- (M1) or anti-inflammatory (M2) functional phenotypes. Furthermore, different stimuli have been associated with differentiation of newly discovered M2 subtypes: IL-4/IL-13 (M2a), immunecomplex (M2b), IL-10/glucocorticoids (M2c), and adenosine receptor agonist (M2d). More recently, additional intraplaque macrophage phenotypes were also recognized in response to CXCL4 (M4), oxidized phospholipids (Mox), haemoglobin/haptoglobin complexes (HAmac/M(Hb)), and heme (Mhem). Such macrophage polarization was described as a progression among multiple phenotypes, which reflect the activity of different transcriptional factors and the cross-talk between intracellular signalling. Finally, the distribution of macrophage subsets within different plaque areas was markedly associated with cardiovascular (CV) vulnerability. The aim of this review is to update the current knowledge on the role of macrophage subsets in atherogenesis. In addition, the molecular mechanisms underlying macrophage phenotypic shift will be summarised and discussed. Finally, the role of intraplaque macrophages as predictors of CV events and the therapeutic potential of these cells will be discussed.

scholarly journals An Updated Insight Into Molecular Mechanism of Hydrogen Sulfide in Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury Under Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Hai-Jian Sun ◽  
Zhi-Yuan Wu ◽  
Xiao-Wei Nie ◽  
Xin-Yu Wang ◽  
Jin-Song Bian
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Protective Effects ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

Cardiovascular diseases are the most common complications of diabetes, and diabetic cardiomyopathy is a major cause of people death in diabetes. Molecular, transcriptional, animal, and clinical studies have discovered numerous therapeutic targets or drugs for diabetic cardiomyopathy. Within this, hydrogen sulfide (H2S), an endogenous gasotransmitter alongside with nitric oxide (NO) and carbon monoxide (CO), is found to play a critical role in diabetic cardiomyopathy. Recently, the protective roles of H2S in diabetic cardiomyopathy have attracted enormous attention. In addition, H2S donors confer favorable effects in myocardial infarction, ischaemia-reperfusion injury, and heart failure under diabetic conditions. Further studies have disclosed that multiplex molecular mechanisms are responsible for the protective effects of H2S against diabetes-elicited cardiac injury, such as anti-oxidative, anti-apoptotic, anti-inflammatory, and anti-necrotic properties. In this review, we will summarize the current findings on H2S biology and pharmacology, especially focusing on the novel mechanisms of H2S-based protection against diabetic cardiomyopathy. Also, the potential roles of H2S in diabetes-aggravated ischaemia-reperfusion injury are discussed.

scholarly journals Caloric restriction mimetics for the treatment of cardiovascular diseases

2020 ◽  
Author(s):  
Sebastiano Sciarretta ◽  
Maurizio Forte ◽  
Francesca Castoldi ◽  
Giacomo Frati ◽  
Francesco Versaci ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Animal Models ◽  
Caloric Restriction ◽  
Molecular Mechanisms ◽  
Relevant Literature ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Beneficial Effects ◽  
Mechanical Overload

Abstract Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis, or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodelling in animal models of ageing, mechanical overload, chronic myocardial ischaemia, and in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischaemia–reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.

scholarly journals Biological markers in risk stratification and progression of cardiovascular disease: present and future

2018 ◽  
Vol 17 (4) ◽  
pp. 264-280 ◽  
Author(s):  
V. L. Ostanko ◽  
T. P. Kalacheva ◽  
E. V. Kalyuzhina ◽  
I. K. Livshits ◽  
A. A. Shalovay ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Early Diagnosis ◽  
Biological Markers ◽  
Molecular Mechanisms ◽  
Biological Marker ◽  
Disease Present ◽  
The Ideal

Taking into account the increase in the level of cardiovascular diseases in recent decades, the clinician faces the task of attempting to make the fastest possible diagnosis of the pathology at its earliest stages. That is why the aim of our work was to identify the main groups of biological markers, and to separate the role of each of them in the assessment of the risk of development, progression and possible complications of cardiovascular diseases. We have given the main working classification of markers of cardiovascular processes with the allocation of their main types, as well as the basic criteria for the “ideal” biological marker. Finally, an attempt was made to structure biomarkers depending on their molecular mechanisms of pathogenesis in the development of a particular pathology. All these data should help the clinician at the stage of early diagnosis of cardiovascular disease.

Protective effects of soy-isoflavones in cardiovascular disease

2008 ◽  
Vol 28 (01/02) ◽  
pp. 85-88 ◽  
Author(s):  
D. Fuchs ◽  
H. Daniel ◽  
U. Wenzel
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Dietary Intervention ◽  
Mononuclear Cells ◽  
Oxidized Ldl ◽  
Proteome Analysis ◽  
Soy Isoflavones ◽  
Protective Effects ◽  
Estrogen Production

SummaryEpidemiological studies indicate that the consumption of soy-containing food may prevent or slow-down the development of cardiovascular disease. In endothelial cells application of a soy extract or a combination of the most abundant soy isoflavones genistein and daidzein both inhibited apoptosis, a driving force in atherosclerosis development, when applied in combination with oxidized LDL or homocysteine. Proteome analysis revealed that the stressorinduced alteration of protein expression profile was reversed by the soy extract or the genistein/daidzein mixture. Only few protein entities that could be functionally linked to mitochondrial dysfunction were regulated in common by both application forms of isoflavones. A dietary intervention with isoflavone-enriched soy extract in postmenopausal women, who generally show strongly increased cardiovascular risk due to diminished estrogen production, led to significant alterations in the steady state levels of proteins from mononuclear blood cells. The proteins identified by proteome analysis revealed that soy isoflavones may increase the anti-inflammatory response in blood mononuclear cells thereby contributing to the atherosclerosispreventive activities of a soy-rich diet. Conclusion: By proteome analysis protein targets were identified in vitro in endothelial cells that respond to soy isoflavones and that may decipher molecular mechanisms through which soy products exert their protective effects in the vasculature.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

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