Cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes

2009 ◽  
Vol 116 (5) ◽  
pp. 377-389 ◽  
Author(s):  
Kou-Gi Shyu
Keyword(s):  
Shear Stress ◽  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Cardiac Myocytes ◽  
Molecular Mechanisms ◽  
Atherosclerotic Lesion ◽  
Mechanical Stretch ◽  
Vascular Cells ◽  
Molecular Effects ◽  
The Impact

Cells in the cardiovascular system are permanently subjected to mechanical forces due to the pulsatile nature of blood flow and shear stress, created by the beating heart. These haemodynamic forces play an important role in the regulation of vascular development, remodelling, wound healing and atherosclerotic lesion formation. Mechanical stretch can modulate several different cellular functions in VSMCs (vascular smooth muscle cells). These functions include, but are not limited to, cell alignment and differentiation, migration, survival or apoptosis, vascular remodelling, and autocrine and paracrine functions. Laminar shear stress exerts anti-apoptotic, anti-atherosclerotic and antithrombotic effects on ECs (endothelial cells). Mechanical stretch of cardiac myocytes can modulate growth, apoptosis, electric remodelling, alterations in gene expression, and autocrine and paracrine effects. The aim of the present review is primarily to summarize the cellular and molecular effects of mechanical stretch on vascular cells and cardiac myocytes, emphasizing the molecular mechanisms underlying the regulation. Knowledge of the impact of mechanical stretch on the cardiovascular system is vital to the understanding of the pathogenesis of cardiovascular diseases, and is also crucial to provide new insights into the prevention and therapy of cardiovascular diseases.

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.

scholarly journals A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression

2021 ◽  
Author(s):  
Victor Delprat ◽  
Carine Michiels
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
The Body ◽  
Vascular Cells ◽  
Tumor Associated Macrophage ◽  
Immune Cell Activation ◽  
The Impact

AbstractCancer progression largely depends on tumor blood vessels as well on immune cell infiltration. In various tumors, vascular cells, namely endothelial cells (ECs) and pericytes, strongly regulate leukocyte infiltration into tumors and immune cell activation, hence the immune response to cancers. Recently, a lot of compelling studies unraveled the molecular mechanisms by which tumor vascular cells regulate monocyte and tumor-associated macrophage (TAM) recruitment and phenotype, and consequently tumor progression. Reciprocally, TAMs and monocytes strongly modulate tumor blood vessel and tumor lymphatic vessel formation by exerting pro-angiogenic and lymphangiogenic effects, respectively. Finally, the interaction between monocytes/TAMs and vascular cells is also impacting several steps of the spread of cancer cells throughout the body, a process called metastasis. In this review, the impact of the bi-directional dialog between blood vascular cells and monocytes/TAMs in the regulation of tumor progression is discussed. All together, these data led to the design of combinations of anti-angiogenic and immunotherapy targeting TAMs/monocyte whose effects are briefly discussed in the last part of this review.

scholarly journals Cardiovascular adaptations to particle inhalation exposure: molecular mechanisms of the toxicology

2020 ◽  
Vol 319 (2) ◽  
pp. H282-H305
Author(s):  
Amina Kunovac ◽  
Quincy A. Hathaway ◽  
Mark V. Pinti ◽  
Andrew D. Taylor ◽  
John M. Hollander
Keyword(s):  
Particulate Matter ◽  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Inhalation Exposure ◽  
Ambient Air ◽  
Consumer Products ◽  
Comprehensive Overview ◽  
Particle Inhalation ◽  
The Impact

Ambient air, occupational settings, and the use and distribution of consumer products all serve as conduits for toxicant exposure through inhalation. While the pulmonary system remains a primary target following inhalation exposure, cardiovascular implications are exceptionally culpable for increased morbidity and mortality. The epidemiological evidence for cardiovascular dysfunction resulting from acute or chronic inhalation exposure to particulate matter has been well documented, but the mechanisms driving the resulting disturbances remain elusive. In the current review, we aim to summarize the cellular and molecular mechanisms that are directly linked to cardiovascular health following exposure to a variety of inhaled toxicants. The purpose of this review is to provide a comprehensive overview of the biochemical changes in the cardiovascular system following particle inhalation exposure and to highlight potential biomarkers that exist across multiple exposure paradigms. We attempt to integrate these molecular signatures in an effort to provide direction for future investigations. This review also characterizes how molecular responses are modified in at-risk populations, specifically the impact of environmental exposure during critical windows of development. Maternal exposure to particulate matter during gestation can lead to fetal epigenetic reprogramming, resulting in long-term deficits to the cardiovascular system. In both direct and indirect (gestational) exposures, connecting the biochemical mechanisms with functional deficits outlines pathways that can be targeted for future therapeutic intervention. Ultimately, future investigations integrating “omics”-based approaches will better elucidate the mechanisms that are altered by xenobiotic inhalation exposure, identify biomarkers, and guide in clinical decision making.

scholarly journals Assessment of the relationship of exacerbations of diseases of the cardiovascular system with the meteorological situation

2021 ◽  
Vol 100 (12) ◽  
pp. 1350-1358
Author(s):  
Natalia M. Kolyagina ◽  
Tat'jana A. Berezhnova ◽  
Nikolaj P. Mamchik ◽  
Oleg V. Klepikov ◽  
Sergej A. Yeprintsev
Keyword(s):  
Cardiovascular Diseases ◽  
Medical Care ◽  
Cardiovascular System ◽  
Atmospheric Pressure ◽  
Meteorological Factors ◽  
Ambient Air ◽  
Medical Assistance ◽  
Meteorological Situation ◽  
The Impact ◽  
The Relationship

Introduction. The impact of weather factors on the occurrence of exacerbations of diseases in meteodependent people is currently one of the actively studied problems of medicine. The aim of the study was to identify the relationship between exacerbations of diseases of the cardiovascular system with the meteorological situation to substantiate the need for preventive and informational work with meteodependent patients. Material and research methods. The study used daily data on the number of patients with cardiovascular diseases seeking medical care at Voronezh City Polyclinic No. 18 and daily information on weather conditions for 2018. The ratio of the average number of cases of medical assistance requests on days unfavourable for meteorological factors to the average number of cases of medical assistance requests per day during the year was calculated. Using software (Statistica Base V6.1), a correlation analysis of the relationship between the number of medical requests and meteorological factors was carried out. Results. It has been established that the appealability of patients with cardiovascular diseases for medical care on days unfavourable for meteorological factors is 1.1-2.0 times higher than the average annual indicator. The most informative characteristic of the six meteorological indicators taken into account in the study (average daily, minimum, maximum ambient air temperature; temperature drops by more than eight °C per day; atmospheric pressure; atmospheric pressure drops by 12 mm Hg per day or more) is a sharp drop in atmospheric pressure during the day, with which statistically significant (p <0.05) correlates the number of cases of patients with cardiovascular diseases seeking medical help. Conclusion. In medical institutions providing primary health care, it is advisable to single out separate groups of patients with meteorological dependence for dynamic observation and conduct information work with them to mitigate the severity of the course of diseases of the cardiovascular system on days unfavourable according to meteorological indicators.

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 Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2730 ◽  
Author(s):  
Diego Estrada-Luna ◽  
María Ortiz-Rodriguez ◽  
Lizett Medina-Briseño ◽  
Elizabeth Carreón-Torres ◽  
Jeannett Izquierdo-Vega ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Density Lipoprotein ◽  
Protein Composition ◽  
Inverse Correlation ◽  
Epidemiological Studies ◽  
High Density ◽  
High Density Lipoproteins ◽  
Current Therapies ◽  
The Impact

High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.

scholarly journals Role of TRP channels in the cardiovascular system

2015 ◽  
Vol 308 (3) ◽  
pp. H157-H182 ◽  
Author(s):  
Zhichao Yue ◽  
Jia Xie ◽  
Albert S. Yu ◽  
Jonathan Stock ◽  
Jianyang Du ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Mechanical Stretch ◽  
Signal Pathways ◽  
Variable Degree ◽  
Cell Functions

The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca2+-permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases.

scholarly journals Тhе features of a personalized approach to the treatment of cardiovascular diseases during pregnancy

2021 ◽  
Vol 25 (3) ◽  
pp. 498-509
Author(s):  
D. G. Konkov ◽  
O. V. Bulavenko ◽  
N. V. Adamchuk ◽  
S. М. Kosianenko
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Animal Studies ◽  
Aortic Disease ◽  
Team Approach ◽  
Cardiovascular Pathology ◽  
Perinatal Pathology ◽  
History Of ◽  
The Impact

Annotation. For the cases of cardiovascular pathology during pregnancy include hypertensive disorders, hypercholesterolemia, myocardial infarction, cardiomyopathy, arrhythmias, valve disease, thromboembolic diseases, aortic disease and cerebrovascular pathology. Cardiovascular disease (CVD) is the leading cause of death from pregnancy in the world. Raising maternal age and comorbid diseases contribute to increased maternal mortality, also. When searching for literature, we used Medline systems from PubMed (2011). The search was adapted for Embase (2015 - 2021) and Scopus (2017 - 2021). Inclusion criteria were as follows: the impact of diseases of the cardiovascular system on pregnancy; the impact of pregnancy on the course of cardiovascular disease; features of diagnosis and prevention of women with CVD at the stage of preconception and during pregnancy; safety of drugs for the treatment of cardiovascular pathology during pregnancy; choice of drugs to prevent perinatal pathology in women with CVD; features of antenatal observation in CVD. We excluded from the study: references to 2011 (more than 10 years); not English; all methods that were not directly related to the pathology of the cardiovascular system during pregnancy; concomitant diseases that can lead to aggravation of pregnancy; animal studies. As a result, 76 studies were identified that were subject to final inclusion in the systematic review. Analysis of the identified literature sources showed that the preconception reproductive strategy to be developed by a multidisciplinary cardio-obstetric team is becoming important for women with a history of cardiovascular disease or for those with a history of familial preeclampsia. Cardio-obstetrics has become as an important multidisciplinary industry that requires a team approach to optimizing the clinical management of cardiovascular disease during pregnancy. Timely involvement of the cardio-obstetric group is crucial to prevent maternal morbidity and mortality during pregnancy and 1 year after delivery. A general understanding of the importance of the impact of cardiovascular disease on pregnancy and the impact of pregnancy on existing CVD should be a basic area of expertise for family medicine professionals, cardiologists, obstetricians and gynecologists. The given scientific and clinical review of sources of evidence-based medicine contains certain features of predictor diagnosis, prevention and treatment of manifested forms of cardiovascular diseases during pregnancy.

scholarly journals Viral Infection and Cardiovascular Disease: Implications for the Molecular Basis of COVID-19 Pathogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 1659
Author(s):  
Sarah Seeherman ◽  
Yuichiro J. Suzuki
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Systemic Hypertension ◽  
Older Individuals ◽  
Mortality And Morbidity ◽  
Coronary Syndrome ◽  
Cardiovascular Comorbidities ◽  
Immunodeficiency Virus

The current pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While this respiratory virus only causes mild symptoms in younger healthy individuals, elderly people and those with cardiovascular diseases such as systemic hypertension are susceptible to developing severe conditions that can be fatal. SARS-CoV-2 infection is also associated with an increased incidence of cardiovascular diseases such as myocardial injury, acute coronary syndrome, and thromboembolism. Understanding the mechanisms of the effects of this virus on the cardiovascular system should thus help develop therapeutic strategies to reduce the mortality and morbidity associated with SARS-CoV-2 infection. Since this virus causes severe and fatal conditions in older individuals with cardiovascular comorbidities, effective therapies targeting specific populations will likely contribute to ending this pandemic. In this review article, the effects of various viruses—including other coronaviruses, influenza, dengue, and human immunodeficiency virus—on the cardiovascular system are described to help provide molecular mechanisms of pathologies associated with SARS-CoV-2 infection and COVID-19. The goal is to provide mechanistic information from the biology of other viral infections in relation to cardiovascular pathologies for the purpose of developing improved vaccines and therapeutic agents effective in preventing and/or treating the acute and long-term consequences of SARS-CoV-2 and COVID-19.

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