scholarly journals Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Yang ◽  
Ying Luan ◽  
Rui-Xia Yuan ◽  
Yi Luan
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Histone Modifications ◽  
Histone Methylation ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Cellular Functions ◽  
Inflammatory Reactions ◽  
High Prevalence

The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.

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.

scholarly journals Physiological role of ROCKs in the cardiovascular system

2006 ◽  
Vol 290 (3) ◽  
pp. C661-C668 ◽  
Author(s):  
Kensuke Noma ◽  
Naotsugu Oyama ◽  
James K. Liao
Keyword(s):  
Protein Kinase ◽  
Cardiovascular System ◽  
Vascular Inflammation ◽  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Kinase Substrate ◽  
Cytoskeleton Organization ◽  
Beneficial Effects ◽  
Actin Cytoskeleton Organization

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

Role for Chemokines in the Vasculopathy Associated with Sickle Cell Dsease and Pulmonary Hypertension

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4804-4804 ◽  
Author(s):  
Anitaben Tailor ◽  
Gregory J. Kato
Keyword(s):  
Sickle Cell ◽  
Vascular Inflammation ◽  
Inverse Correlation ◽  
Inflammatory Protein ◽  
Potential Marker ◽  
Increased Risk ◽  
High Prevalence ◽  
Pulmonary Arterial

Abstract Sickle cell disease (SCD) is a hemolytic disorder characterized by transient vaso-occlusive crisis (VOC). Moreover, there is a high prevalence of SCD-associated pulmonary arterial hypertension (PAH), indicated by a tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/sec, leading to increased risk for early mortality. Monocytes have been proposed as pivotal cells in vascular inflammation in animal models of SCD. Preliminary studies in our group have shown a potential role for monocyte chemokines in the vasculopathy of SCD. The objective of this study is to investigate the role of two chemokines: regulated upon activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein-1β (MIP-1β) in SCD and SCD-associated PAH. Plasma samples were collected from patients with SCD at steady state and from healthy African-American control subjects. Plasma levels of RANTES and MIP-1β were measured using an enzyme immunoassay system. Patients with SCD exhibited significantly higher levels of both MIP-1β (median 465.3 vs. 398.5 pg/ml, p<0.0001) and RANTES (median 47774 vs. 17445pg/ml, p<0.0004) than healthy controls. Further characterization of SCD patients with or without PAH demonstrated that whereas MIP-1β exhibited no correlation with PAH, RANTES demonstrated an inverse correlation with PAH (r= −0.25, p<0.03) with significance achieved in patients that exhibited severe PAH (TRV> 2.9, p<0.05). These findings suggest that both chemokines, RANTES and MIP-1β, are associated with the vasculopathy of SCD, and whereas MIP-1β does not appear to be associated with SCD-associated PAH, RANTES levels are inversely correlated to the severity of PAH. RANTES merits further investigation as a potential marker in PAH, and for a possible role in its progression.

scholarly journals Seaweeds as Preventive Agents for Cardiovascular Diseases: From Nutrients to Functional Foods

Marine Drugs ◽  
2015 ◽  
Vol 13 (11) ◽  
pp. 6838-6865 ◽  
Author(s):  
Susana Cardoso ◽  
Olívia Pereira ◽  
Ana Seca ◽  
Diana Pinto ◽  
Artur Silva
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Functional Foods ◽  
Cardiovascular Health ◽  
Vascular Inflammation ◽  
Dietary Fibers ◽  
Health Promoting ◽  
Reported Data ◽  
Cardiovascular Health Promotion

Being naturally enriched in key nutrients and in various health-promoting compounds, seaweeds represent promising candidates for the design of functional foods. Soluble dietary fibers, peptides, phlorotannins, lipids and minerals are macroalgae’s major compounds that can hold potential in high-value food products derived from macroalgae, including those directed to the cardiovascular-health promotion. This manuscript revises available reported data focusing the role of diet supplementation of macroalgae, or extracts enriched in bioactive compounds from macroalgae origin, in targeting modifiable markers of cardiovascular diseases (CVDs), like dyslipidemia, oxidative stress, vascular inflammation, hypertension, hypercoagulability and activation of the sympathetic and renin-angiotensin systems, among others. At last, the review also describes several products that have been formulated with the use of whole macroalgae or extracts, along with their claimed cardiovascular-associated benefits.

scholarly journals Recent progress in research on molecular mechanisms of autophagy in the heart

2015 ◽  
Vol 308 (4) ◽  
pp. H259-H268 ◽  
Author(s):  
Yasuhiro Maejima ◽  
Yun Chen ◽  
Mitsuaki Isobe ◽  
Åsa B. Gustafsson ◽  
Richard N. Kitsis ◽  
...  
Keyword(s):  
Heart Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Degradation Process ◽  
Structure And Function ◽  
Cellular Functions ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Cellular Dysfunction

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.

scholarly journals Resolving the Ionotropic P2X4 Receptor Mystery Points towards a New Therapeutic Target for Cardiovascular Diseases

2020 ◽  
Vol 21 (14) ◽  
pp. 5005 ◽  
Author(s):  
Bruno Bragança ◽  
Paulo Correia-de-Sá
Keyword(s):  
Clinical Practice ◽  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
State Of The Art ◽  
P2x4 Receptor ◽  
Extracellular Milieu ◽  
Intracellular Energy ◽  
Further Development ◽  
Cardiovascular Functions

Adenosine triphosphate (ATP) is a primordial versatile autacoid that changes its role from an intracellular energy saver to a signaling molecule once released to the extracellular milieu. Extracellular ATP and its adenosine metabolite are the main activators of the P2 and P1 purinoceptor families, respectively. Mounting evidence suggests that the ionotropic P2X4 receptor (P2X4R) plays pivotal roles in the regulation of the cardiovascular system, yet further therapeutic advances have been hampered by the lack of selective P2X4R agonists. In this review, we provide the state of the art of the P2X4R activity in the cardiovascular system. We also discuss the role of P2X4R activation in kidney and lungs vis a vis their interplay to control cardiovascular functions and dysfunctions, including putative adverse effects emerging from P2X4R activation. Gathering this information may prompt further development of selective P2X4R agonists and its translation to the clinical practice.

scholarly journals Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand

2018 ◽  
Vol 10 (466) ◽  
pp. eaau7137 ◽  
Author(s):  
Julia Luther ◽  
Timur Alexander Yorgan ◽  
Tim Rolvien ◽  
Lorenz Ulsamer ◽  
Till Koehne ◽  
...  
Keyword(s):  
Bone Mass ◽  
Early Onset ◽  
Therapeutic Potential ◽  
Bone Fractures ◽  
Treatment Of Osteoporosis ◽  
High Prevalence ◽  
And Function ◽  
Mass Increase ◽  
Bone Mass Regulation

WNT1mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygousWNT1mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass increase in developing young, adult, and aged mice by rapidly increasing osteoblast numbers and function. Contrary to current mechanistic models, loss of Lrp5, the co-receptor thought to transmit extracellular WNT signals during bone mass regulation, did not reduce the bone-anabolic effect of Wnt1, providing direct evidence that Wnt1 function does not require the LRP5 co-receptor. The identification of Wnt1 as a regulator of bone formation and remodeling provides the basis for development of Wnt1-targeting drugs for the treatment of osteoporosis.

scholarly journals Post-Translational S-Nitrosylation of Proteins in Regulating Cardiac Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1051 ◽  
Author(s):  
Xiaomeng Shi ◽  
Hongyu Qiu
Keyword(s):  
Therapeutic Potential ◽  
Heart Diseases ◽  
Redox Homeostasis ◽  
Redox Status ◽  
Cardiac Protection ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Redox ◽  
Novel Therapeutic Strategies

Like other post-translational modifications (PTMs) of proteins, S-nitrosylation has been considered a key regulatory mechanism of multiple cellular functions in many physiological and disease conditions. Emerging evidence has demonstrated that S-nitrosylation plays a crucial role in regulating redox homeostasis in the stressed heart, leading to discoveries in the mechanisms underlying the pathogenesis of heart diseases and cardiac protection. In this review, we summarize recent studies in understanding the molecular and biological basis of S-nitrosylation, including the formation, spatiotemporal specificity, homeostatic regulation, and association with cellular redox status. We also outline the currently available methods that have been applied to detect S-nitrosylation. Additionally, we synopsize the up-to-date studies of S-nitrosylation in various cardiac diseases in humans and animal models, and we discuss its therapeutic potential in cardiac protection. These pieces of information would bring new insights into understanding the role of S-nitrosylation in cardiac pathogenesis and provide novel avenues for developing novel therapeutic strategies for heart diseases.

scholarly journals Role of Peroxisome Proliferator-Activated Receptor-γin Vascular Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kousei Ohshima ◽  
Masaki Mogi ◽  
Masatsugu Horiuchi
Keyword(s):  
Immune Cells ◽  
Adipocyte Differentiation ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Important Regulator ◽  
Artery Disease

Vascular inflammation plays a crucial role in atherosclerosis, and its regulation is important to prevent cerebrovascular and coronary artery disease. The inflammatory process in atherogenesis involves a variety of immune cells including monocytes/macrophages, lymphocytes, dendritic cells, and neutrophils, which all express peroxisome proliferator-activated receptor-γ(PPAR-γ). PPAR-γis a nuclear receptor and transcription factor in the steroid superfamily and is known to be a key regulator of adipocyte differentiation. Increasing evidence from mainly experimental studies has demonstrated that PPAR-γactivation by endogenous and synthetic ligands is involved in lipid metabolism and anti-inflammatory activity. In addition, recent clinical studies have shown a beneficial effect of thiazolidinediones, synthetic PPAR-γligands, on cardiovascular disease beyond glycemic control. These results suggest that PPAR-γactivation is an important regulator in vascular inflammation and is expected to be a therapeutic target in the treatment of atherosclerotic complications. This paper reviews the recent findings of PPAR-γinvolvement in vascular inflammation and the therapeutic potential of regulating the immune system in atherosclerosis.

scholarly journals microRNAs in the onset and development of cardiovascular disease

2013 ◽  
Vol 126 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Kasey C. Vickers ◽  
Kerry-Anne Rye ◽  
Fatiha Tabet
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Present Review ◽  
Novel Therapies ◽  
Regulatory Processes ◽  
Gene Regulatory

Physiological and pathological roles for small non-encoding miRNAs (microRNAs) in the cardiovascular system have recently emerged and are now widely studied. The discovery of widespread functions of miRNAs has increased the complexity of gene-regulatory processes and networks in both the cardiovascular system and cardiovascular diseases. Indeed, it has recently been shown that miRNAs are implicated in the regulation of many of the steps leading to the development of cardiovascular disease. These findings represent novel aspects in miRNA biology and, therefore, our understanding of the role of these miRNAs during the pathogenesis of cardiovascular disease is critical for the development of novel therapies and diagnostic interventions. The present review will focus on understanding how miRNAs are involved in the onset and development of cardiovascular diseases.

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