scholarly journals Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7462
Author(s):  
Mirna S. Sadek ◽  
Eleder Cachorro ◽  
Ali El-Armouche ◽  
Susanne Kämmerer
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Comprehensive Overview ◽  
Therapeutic Implications ◽  
Secondary Messengers ◽  
Cgmp Signaling ◽  
Cardiovascular Pathologies ◽  
Regulatory Functions ◽  
Cellular Components ◽  
Camp And Cgmp

Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3′,5′-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases (CVDs). PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signaling with cardioprotective cGMP signaling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2- mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

scholarly journals Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

2020 ◽  
Author(s):  
Mirna S. Sadek ◽  
Eleder Cachorro ◽  
Susanne Kämmerer ◽  
Ali El-Armouche
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Potential Therapeutic Target ◽  
Comprehensive Overview ◽  
Therapeutic Implications ◽  
Secondary Messengers ◽  
Cardiovascular Pathologies ◽  
Regulatory Functions ◽  
Cellular Components ◽  
Camp And Cgmp

Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3’,5’-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases. PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signalling with cardioprotective cGMP signalling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2 mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

scholarly journals Mitochondrial Transfer in Cardiovascular Disease: From Mechanisms to Therapeutic Implications

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun Chen ◽  
Jinjie Zhong ◽  
Lin-lin Wang ◽  
Ying-ying Chen
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
System Development ◽  
Critical Role ◽  
Extracellular Vesicle ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Mitochondrial Transfer ◽  
Transfer Strategies

Mitochondrial dysfunction has been proven to play a critical role in the pathogenesis of cardiovascular diseases. The phenomenon of intercellular mitochondrial transfer has been discovered in the cardiovascular system. Studies have shown that cell-to-cell mitochondrial transfer plays an essential role in regulating cardiovascular system development and maintaining normal tissue homeostasis under physiological conditions. In pathological conditions, damaged cells transfer dysfunctional mitochondria toward recipient cells to ask for help and take up exogenous functional mitochondria to alleviate injury. In this review, we summarized the mechanism of mitochondrial transfer in the cardiovascular system and outlined the fate and functional role of donor mitochondria. We also discussed the advantage and challenges of mitochondrial transfer strategies, including cell-based mitochondrial transplantation, extracellular vesicle-based mitochondrial transplantation, and naked mitochondrial transplantation, for the treatment of cardiovascular disorders. We hope this review will provide perspectives on mitochondrial-targeted therapeutics in cardiovascular diseases.

scholarly journals Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2436
Author(s):  
Kathrin Broekmans ◽  
Jan Giesen ◽  
Lukas Menges ◽  
Doris Koesling ◽  
Michael Russwurm
Keyword(s):  
Cardiovascular System ◽  
Cardiac Remodeling ◽  
Interstitial Fibrosis ◽  
Therapeutic Implications ◽  
Cgmp Signaling ◽  
Mrna Content ◽  
Perivascular Area ◽  
Cardiovascular Fibrosis ◽  
The Impact ◽  
Deficient Mice

In the NO/cGMP signaling cascade, relevant in the cardiovascular system, two NO-sensitive guanylyl cyclase (NO-GC) isoforms are responsible for NO-dependent cGMP generation. Here, the impact of the major NO-GC isoform, NO-GC1, on fibrosis development in the cardiovascular system was studied in NO-GC1-deficient mice treated with AngiotensinII (AngII), known to induce vascular and cardiac remodeling. Morphometric analysis of NO-GC1 KO’s aortae demonstrated an enhanced increase of perivascular area after AngII treatment accompanied by a higher aortic collagen1 mRNA content. Increased perivascular fibrosis also occurred in cardiac vessels of AngII-treated NO-GC1 KO mice. In line, AngII-induced interstitial fibrosis was 32% more pronounced in NO-GC1 KO than in WT myocardia associated with a higher cardiac Col1 and other fibrotic marker protein content. In sum, increased perivascular and cardiac interstitial fibrosis together with the enhanced collagen1 mRNA content in AngII-treated NO-GC1-deficient mice represent an exciting manifestation of antifibrotic properties of cGMP formed by NO-GC1, a finding with great pharmaco-therapeutic implications.

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

Does HbA1cc Play a Role in the Development of Cardiovascular Diseases?

2018 ◽  
Vol 24 (24) ◽  
pp. 2876-2882 ◽  
Author(s):  
Kailash Prasad
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Half Life ◽  
Serum Levels ◽  
Serum Glucose ◽  
Cvd Risk ◽  
Factors Affecting ◽  
Diagnosis And Management ◽  
Coronary Artery Atherosclerosis

Cardiovascular diseases (CVD) may be mediated through increases in the cardiovascular risk factors. Hemoglobin A1c (HbA1c) also called glycated hemoglobin is presently used for the diagnosis and management of diabetes. It has adverse effects on cardiovascular system. This review deals with its synthesis and effects on the cardiovascular system. The serum levels of HbA1c have been reported to be affected by various factors including, the lifespan of erythrocytes, factors affecting erythropoiesis, agents interfering glycation of Hb, destruction of erythrocytes, drugs that shift the formation of Hb, statins, and drugs interfering the HbA1c assay. Levels of HbA1c are positively correlated with serum glucose and advanced glycation end products ( AGE), but no correlation between AGE and serum glucose. AGE cannot replace HbA1c for the diagnosis and management of diabetes because there is no correlation of AGE with serum glucose, and because the half-life of protein with which glucose combines is only 14-20 days as compared to erythrocytes which have a half-life of 90-120 days. HbA1c is positively associated with CVD such as the carotid and coronary artery atherosclerosis, ischemic heart disease, ischemic stroke and hypertension.HbA1c induces dyslipidemia, hyperhomocysteinemia, and hypertension, and increases C-reactive protein, oxidative stress and blood viscosity that would contribute to the development of cardiovascular diseases. In conclusion, HbA1c serves as a useful marker for the diagnosis and management of diabetes. AGE cannot replace HbA1c in the diagnosis and management of diabetes. There is an association of HbA1c with CVD which be mediated through modulation of CVD risk factors.

scholarly journals Glutathione Participation in the Prevention of Cardiovascular Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1220
Author(s):  
Deyamira Matuz-Mares ◽  
Héctor Riveros-Rosas ◽  
María Magdalena Vilchis-Landeros ◽  
Héctor Vázquez-Meza
Keyword(s):  
Cardiovascular Diseases ◽  
Superoxide Anion ◽  
Reactive Nitrogen Species ◽  
Hypochlorous Acid ◽  
Reduced Glutathione ◽  
Heart Diseases ◽  
Reactive Species ◽  
Oxygen Species ◽  
Cardiovascular Pathologies

Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular pathologies, during their development, generate a state of oxidative stress that leads to a deterioration in the patient’s conditions associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Within these reactive species we find superoxide anion (O2•–), hydroxyl radical (•OH), nitric oxide (NO•), as well as other species of non-free radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HClO) and peroxynitrite (ONOO–). A molecule that actively participates in counteracting the oxidizing effect of reactive species is reduced glutathione (GSH), a tripeptide that is present in all tissues and that its synthesis and/or regeneration is very important to be able to respond to the increase in oxidizing agents. In this review, we will address the role of glutathione, its synthesis in both the heart and the liver, and its importance in preventing or reducing deleterious ROS effects in cardiovascular diseases.

SIGNIFICANCE OF PLATELETS IN INFLAMMATORY AND THROMBOTIC REACTIONS IN THE ELDERLY

2021 ◽  
pp. 76-83
Author(s):  
А. М. Осадчук ◽  
И. Л. Давыдкин ◽  
И. А. Золотовская
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Antiplatelet Therapy ◽  
Plasma Levels ◽  
The Elderly ◽  
Wide Audience ◽  
Hemostatic System ◽  
Clinical Consequences ◽  
Coronavirus Infection ◽  
System Today

Развитие тромботических реакций, приводящих к нежелательным клиническим последствиям у лиц пожилого возраста, известно при многих заболеваниях, включая патологию сердечно-сосудистой системы. Сегодня идет накопление данных о степени выраженности изменений системы гемостаза у пациентов с новой коронавирусной инфекцией (COVID-19) и изучение тромбоцитарного и плазменного звена. Для понимания некоторых механизмов, связанных с патологией тромбоцитов, нами представлен обзор, в котором обобщены сведения о патофизиологических реакциях тромбоцитов в условиях их старения и возможных механизмах их патологической агрегации. Возможно, представленные фундаментальные и клинические данные будут интересны широкой аудитории специалистов для обсуждения ранней антитромбоцитарной терапии и ее обоснования не только у пациентов с сердечно-сосудистыми заболеваниями, но и с COVID-19. The development of thrombotic reactions that lead to undesirable clinical consequences in the elderly is known in many diseases, including pathology of the cardiovascular system. Today, data on the severity of changes in the hemostatic system in patients with a new coronavirus infection (COVID-19) and the study of platelet and plasma levels are being accumulated. In order to understand some of the mechanisms associated with platelet pathology, we present a review that summarizes information about the pathophysiological reactions of platelets in the conditions of their aging and possible mechanisms of their pathological aggregation. Perhaps the presented fundamental and clinical data will be of interest to a wide audience of specialists to discuss early antiplatelet therapy and its justification not only in patients with cardiovascular diseases, but also with COVID-19.

scholarly journals Advances and Perspectives of Light-gated Phosphodiesterases for Optogenetic Applications

2020 ◽  
Author(s):  
Yuehui Tian ◽  
Shang Yang ◽  
Shiqiang Gao
Keyword(s):  
Intracellular Signaling ◽  
Second Messengers ◽  
Cell Physiology ◽  
Intracellular Camp ◽  
Animal Cells ◽  
Signaling Mechanism ◽  
Surface Receptors ◽  
Cgmp Signaling ◽  
Pros And Cons ◽  
Camp And Cgmp

Second messengers, cyclic adenosine 3'-5'-monophosphate (cAMP) and cyclic guanosine 3'-5'-monophosphate (cGMP) are playing important roles in many animal cells by regulating intracellular signaling pathways and modulating cell physiology. Environmental cues like temperature, light and chemical compounds can stimulate cell surface receptors and trigger the generation of second messengers and the following regulations. Spread of cAMP and cGMP is further shaped by cyclic nucleotide phosphodiesterases (PDEs) for orchestration of intracellular microdomain signaling. However, localized intracellular cAMP and cGMP signaling requires further investigation. Optogenetic manipulation of cAMP and cGMP offers new opportunities of spatio-temporally precise study of their signaling mechanism. Light-gated nucleotide cyclases are well developed and applied for cAMP/cGMP manipulation. Recently discovered rhodopsin phosphodiesterase gene from protists established new and direct biological connection between light and PDEs. Light-regulated PDEs are under development and of demand to complete the toolkit of cAMP/cGMP manipulation. In this review, we summarize the state of the art, pros and cons of artificial and natural light-regulated PDEs and discuss potential new strategies of developing light-gated PDEs for optogenetic manipulation.

scholarly journals Diyette Proteinler, Aminoasitler ve Bazı Diğer Aminli Bileşiklerin Kardiyovasküler Sistem Üzerine Metabolik Etkileri

2017 ◽  
Vol 5 (1) ◽  
pp. 71
Author(s):  
Elif Uğur ◽  
Reyhan Nergiz Ünal
Keyword(s):  
Amino Acids ◽  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Cardiovascular Health ◽  
Aromatic Amino Acids ◽  
Protein Composition ◽  
Vital Role ◽  
Heterocyclic Aromatic Amines ◽  
Cause Of Deaths ◽  
One Carbon Metabolism

During the prevention and treatment of cardiovascular diseases, first cause of deaths in the world, diet has a vital role. While nutrition programs for the cardiovascular health generally focus on lipids and carbohydrates, effects of proteins are not well concerned. Thus this review is written in order to examine effect of proteins, amino acids, and the other amine consisting compounds on cardiovascular system. Because of that animal or plant derived proteins have different protein composition in different foods such as dairy products, egg, meat, chicken, fish, pulse and grains, their effects on blood pressure and regulation of lipid profile are unlike. In parallel amino acids made up proteins have different effect on cardiovascular system. From this point, sulfur containing amino acids, branched chain amino acids, aromatic amino acids, arginine, ornithine, citrulline, glycine, and glutamine may affect cardiovascular system in different metabolic pathways. In this context, one carbon metabolism, synthesis of hormone, stimulation of signaling pathways and effects of intermediate and final products that formed as a result of amino acids metabolism is determined. Despite the protein and amino acids, some other amine consisting compounds in diet include trimethylamine N-oxide, heterocyclic aromatic amines, polycyclic aromatic hydrocarbons and products of Maillard reaction. These amine consisting compounds generally increase the risk for cardiovascular diseases by stimulating oxidative stress, inflammation, and formation of atherosclerotic plaque.

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