scholarly journals Natriuretic Peptides in the Cardiovascular System: Multifaceted Roles in Physiology, Pathology and Therapeutics

2019 ◽  
Vol 20 (16) ◽  
pp. 3991 ◽  
Author(s):  
Speranza Rubattu ◽  
Massimo Volpe
Keyword(s):  
Cardiovascular System ◽  
Natriuretic Peptides ◽  
Molecular Mechanisms ◽  
Therapeutic Approaches ◽  
Physiological Control ◽  
Physiological Regulation ◽  
Cardiovascular Damage ◽  
Therapeutic Tools ◽  
Kidney Functions ◽  
Current Special Issue

The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. The discovery of NPs provided a fundamental contribution into our understanding of the physiological regulation of blood pressure, and of heart and kidney functions. NPs have also been implicated in the pathogenesis of several cardiovascular diseases (CVDs), including hypertension, atherosclerosis, heart failure, and stroke. A fine comprehension of the molecular mechanisms dependent from NPs and underlying the promotion of cardiovascular damage has contributed to improve our understanding of the molecular basis of all major CVDs. Finally, the opportunity to target NPs in order to develop new therapeutic tools for a better treatment of CVDs has been developed over the years. The current Special Issue of the Journal covers all major aspects of the molecular implications of NPs in physiology and pathology of the cardiovascular system, including NP-based therapeutic approaches.

Decoding resistant hypertension signalling pathways

2017 ◽  
Vol 131 (23) ◽  
pp. 2813-2834 ◽  
Author(s):  
Ricardo Cambraia Parreira ◽  
Leandro Heleno Guimarães Lacerda ◽  
Rebecca Vasconcellos ◽  
Swiany Silveira Lima ◽  
Anderson Kenedy Santos ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Signalling Pathways ◽  
Transcriptional Level ◽  
Cardiovascular Damage ◽  
Current State ◽  
Cardiovascular Morbidity And Mortality ◽  
Non Coding Rnas ◽  
Therapeutic Tools

Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin–angiotensin–aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches.

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.

Astrocytes in health and disease

2007 ◽  
Vol 148 (15) ◽  
pp. 697-702 ◽  
Author(s):  
Marianna Murányi ◽  
Zsombor Lacza
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Free Radicals ◽  
Molecular Mechanisms ◽  
Neuronal Dysfunction ◽  
Supporting Cells ◽  
Neuronal Synapses ◽  
Health And Disease ◽  
Novel Targets ◽  
Therapeutic Tools

It is now known that astrocytes are not merely supporting cells but they also play an important role in neuronal funcions. Astrocytes tightly ensheat neuronal synapses and regulate the excitation of neurons by uptaking neurotransmitters; reglulate the cerebral blood flow, cerebral fluid volume and extracellular concentrations of ions. They also supply fuel in the form of lactate and provide free radical scavangers such as glutathione for active neurons. These facts indicate that impaired function of astrocytes may lead to neuronal dysfunction. After brain injury (stroke, trauma or tumors) astrocytes are swollen and release active molecules such as glutamate or free radicals resulting in neuronal dysfunction. Thus, investigation of the molecular mechanisms of astrocyte function may reveal novel targets for the development of therapeutic tools in neuronal diseases.

Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels in the Cardiovascular System

2004 ◽  
Vol 101 (2) ◽  
pp. 390-398 ◽  
Author(s):  
Takashi Kawano ◽  
Shuzo Oshita ◽  
Akira Takahashi ◽  
Yasuo Tsutsumi ◽  
Yoshinobu Tomiyama ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Adenosine Triphosphate ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Transmembrane Domain ◽  
Katp Channels ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Sulfonylurea Receptor ◽  
Inhibitory Effects

Background Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. Methods The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Results Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Conclusions Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.

scholarly journals Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yuefei Jin ◽  
Wangquan Ji ◽  
Haiyan Yang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Endothelial Activation ◽  
World Health ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapeutic Implications ◽  
Endothelial Inflammation ◽  
The World ◽  
Health Organization

AbstractOn 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients. Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation. Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier, promoting pro-coagulative state, inducing endothelial inflammation, and even mediating leukocyte infiltration. This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.

scholarly journals Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 332
Author(s):  
Valentina Brillo ◽  
Leonardo Chieregato ◽  
Luigi Leanza ◽  
Silvia Muccioli ◽  
Roberto Costa
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Eukaryotic Cells ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Lipid Trafficking ◽  
Mitochondrial Ros ◽  
Intracellular Organelles ◽  
Proliferation Regulation ◽  
Dynamic Plasticity

Mitochondria are key intracellular organelles involved not only in the metabolic state of the cell, but also in several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these organelles are characterized by continuous events of fission and fusion which contribute to the dynamic plasticity of their network, also strongly influenced by mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount of reactive oxygen species (ROS) inside eukaryotic cells, which are reported to mediate a plethora of both physiological and pathological cellular functions, such as growth and proliferation, regulation of autophagy, apoptosis, and metastasis. Therefore, targeting mitochondrial ROS could be a promising strategy to overcome and hinder the development of diseases such as cancer, where malignant cells, possessing a higher amount of ROS with respect to healthy ones, could be specifically targeted by therapeutic treatments. In this review, we collected the ultimate findings on the blended interplay among mitochondrial shaping, mitochondrial ROS, and several signaling pathways, in order to contribute to the dissection of intracellular molecular mechanisms involved in the pathophysiology of eukaryotic cells, possibly improving future therapeutic approaches.

Schwannomas of the Nose and Paranasal Sinuses

1993 ◽  
Vol 7 (2) ◽  
pp. 59-65 ◽  
Author(s):  
John R. Wanamaker ◽  
Hayes H. Wanamaker ◽  
Bernard Kotton ◽  
Greg D. Akers ◽  
Pierre Lavertu
Keyword(s):  
Paranasal Sinuses ◽  
Clinical Presentation ◽  
Clinical Course ◽  
Diagnostic Techniques ◽  
Therapeutic Approaches ◽  
Management Philosophy ◽  
Nose And Paranasal Sinuses ◽  
Therapeutic Tools ◽  
Diagnostic Work ◽  
Work Up

Schwannomas are benign neoplasms arising from the peripheral nerve sheath. The sinonasal tract is an unusual location for these neoplasms. Because of their rarity, few series have been reported. Five previously unreported cases of schwannomas of the nose and paranasal sinuses are presented that illustrate the spectrum of disease. The clinical presentation, diagnostic work-up, clinical course, and diverse therapeutic approaches will be discussed. A management philosophy based on the diversity of these tumors and their clinical behavior, and incorporating the new diagnostic and therapeutic tools available to the clinician will be presented. The implications of newer diagnostic techniques including sinonasal endoscopy, magnetic resonance imaging, and immuno-chemistry in the diagnosis and treatment of these tumors will be discussed.

scholarly journals Physiological Regulation of G Protein-Linked Signaling

1999 ◽  
Vol 79 (4) ◽  
pp. 1373-1430 ◽  
Author(s):  
Andrew J. Morris ◽  
Craig C. Malbon
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Chemokine Receptors ◽  
Transcriptional Control ◽  
Heterotrimeric G Proteins ◽  
Protein Prenylation ◽  
Physiological Control ◽  
Physiological Regulation ◽  
Surface Receptors ◽  
Genes Encoding

Heterotrimeric G proteins in vertebrates constitute a family molecular switches that transduce the activation of a populous group of cell-surface receptors to a group of diverse effector units. The receptors include the photopigments such as rhodopsin and prominent families such as the adrenergic, muscarinic acetylcholine, and chemokine receptors involved in regulating a broad spectrum of responses in humans. Signals from receptors are sensed by heterotrimeric G proteins and transduced to effectors such as adenylyl cyclases, phospholipases, and various ion channels. Physiological regulation of G protein-linked receptors allows for integration of signals that directly or indirectly effect the signaling from receptor→G protein→effector(s). Steroid hormones can regulate signaling via transcriptional control of the activities of the genes encoding members of G protein-linked pathways. Posttranscriptional mechanisms are under physiological control, altering the stability of preexisting mRNA and affording an additional level for regulation. Protein phosphorylation, protein prenylation, and proteolysis constitute major posttranslational mechanisms employed in the physiological regulation of G protein-linked signaling. Drawing upon mechanisms at all three levels, physiological regulation permits integration of demands placed on G protein-linked signaling.

Electroimmunoassay of alpha-2-opsonic protein during reticuloendothelial blockade

1977 ◽  
Vol 232 (3) ◽  
pp. R80-R87 ◽  
Author(s):  
F. Blumenstock ◽  
P. Weber ◽  
T. M. Saba ◽  
R. Laffin
Keyword(s):  
Serum Concentration ◽  
Phagocytic Activity ◽  
Lipid Emulsion ◽  
Protein Concentration ◽  
Normal Values ◽  
Serum Levels ◽  
Physiological Control ◽  
Opsonic Activity ◽  
Physiological Regulation ◽  
Monospecific Antiserum

Physiological regulation of reticuloendothelial (RE) phagocytic activity by a plasma opsonic factor has been documented. In the recent study, serum levels of this alpha-2-opsonic protein in rats during colloid-induced RE blockade were measured utilizing an electroimmunoassay (Rocket immunoelectrophoresis) with monospecific antiserum to the purified alpha-2-glycoprotein. RE blockade was produced by the intravenous injection of the gelatinized "RE-test-lipid emulsion" at a dose of 50 mg/100 g body wt. The opsonic activity of serum at various intervals during colloid-induced RE blockade as measured by tissue slice bioassay manifested a high correlation (r = 0.98) with the serum opsonic protein concentration as measured by the electroimmunoassay. During RE blockade (30 min), there was a rapid depletion of the opsonic alpha-2-glycoprotein to 20% of the initial preinjection levels. Serum concentration of this glycoprotein remained low for at least 2-3 h after which time its concentration progressively increased with approximation of normal values by 6 h postblockade. Opsonic protein concentration at 24 h postinjection were significantly (P less than 0.05) elevated above controls. Thus, colloid-induced RE blockade is associated with the removal of this glycoprotein from the serum and recovery from RE blockade is accompanied by a restoration of opsonin levels. The electroimmunoassay can provide a sensitive technique to monitor this humoral factor known to exert a physiological control on the RE system.

scholarly journals Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches

2015 ◽  
pp. 57-74 ◽  
Author(s):  
George Hajishengallis ◽  
Tomoki Maekawa ◽  
Toshiharu Abe ◽  
Evlambia Hajishengallis ◽  
John D. Lambris
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Approaches
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