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.

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.

Current Drug Nano-targeting Strategies for Improvement in the Diagnosis and Treatment of Prevalent Pathologies such as Cardiovascular and Renal Diseases

2019 ◽  
Vol 20 (14) ◽  
pp. 1496-1504 ◽  
Author(s):  
Virna Margarita Martín Giménez ◽  
Lucía Beatriz Fuentes ◽  
Diego Enrique Kassuha ◽  
Walter Manucha
Keyword(s):  
Cardiovascular Diseases ◽  
Side Effects ◽  
Contrast Agent ◽  
Cardiovascular System ◽  
Blood Vessels ◽  
Renal Cancer ◽  
Molecular Targets ◽  
Renal Diseases ◽  
Treatment And Diagnosis ◽  
New Molecular Targets

Background: The kidney and cardiovascular system are closely related to each other during the modulation of the cardiovascular homeostasis. However, the search for new alternatives for the treatment and diagnosis of cardiovascular diseases does not take into account this relationship, so their evaluation results and the advantages offered by their global and integrative analysis are wasted. For example, a variety of receptors that are overexpressed in both pathologies is large enough to allow expansion in the search for new molecular targets and ligands. Nanotechnology offers pharmacological targeting strategies to kidney, heart, and blood vessels for overcoming one of the essential restrictions of traditional cardiovascular therapies the ones related to their unspecific pharmacodynamics distribution in these critical organs. Recent Findings: Drug or contrast agent nano-targeting for treatment or diagnosis of atherosclerosis, thrombosis, renal cancer or fibrosis, glomerulonephritis, among other renal, cardiac and blood vessels pathologies would allow an increase in their efficacy and a reduction of their side effects. Such effects are possible because, through pharmacological targeting, the drug is mainly found at the desired site. Review Purpose: In this mini-review, active, passive, and physical targeting strategies of several nanocarriers that have been assessed and proposed for the treatment and diagnosis of different cardiovascular diseases, are being addressed.

scholarly journals Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 892
Author(s):  
Zaida Abad-Jiménez ◽  
Sandra López-Domènech ◽  
Rubén Díaz-Rúa ◽  
Francesca Iannantuoni ◽  
Segundo Ángel Gómez-Abril ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Low Grade ◽  
Obese Patients ◽  
Visceral Adipose

Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.

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 Therapeutic Interventions of Cardamom in Cancer and Other Human Diseases

2020 ◽  
pp. 74-84
Author(s):  
Samir Qiblawi ◽  
Mohd Adnan Kausar ◽  
S. M. A. Shahid ◽  
Mohd. Saeed ◽  
Awfa Y. Alazzeh
Keyword(s):  
Biological Activity ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Bioactive Constituents ◽  
Active Components ◽  
Inflammatory Conditions ◽  
Multifunctional Compounds ◽  
The World ◽  
Digestive Disorders

Cardamom, a dietary phytoproduct, is the most popular spice in the world, and its beneficial health properties are gaining more and more attention. Small cardamom [Elettaria cardamomum (L.) Maton. (Family: Zingiberaceae) ] has been used for traditional therapeutic applications, including the management of asthma, teeth and gum infections, cataracts, nausea, diarrhea and heart, digestive and kidney disorders. Numerous studies have demonstrated the biological activity of cardamom and its polyphenols, including antioxidant, anti-tumor, anti-inflammatory, and metabolic control.1,8-cineole, and its esters, Limonene, α-terpinyl acetates are the most abundant bioactive constituents in cardamom. They are known to be multifunctional compounds that can be efficient in the prevention or treatment of various types of cancers, cardiovascular diseases, chronic inflammatory conditions, digestive disorders, as well as infectious bacterial and fungal diseases. In this review, we summarized the up-to-date research and underlying molecular mechanisms of cardamom and its active components.

scholarly journals Age-related cerebral small vessel disease and inflammaging

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Tiemei Li ◽  
Yinong Huang ◽  
Wei Cai ◽  
Xiaodong Chen ◽  
Xuejiao Men ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Small Vessel Disease ◽  
Vascular Inflammation ◽  
Regional Analysis ◽  
Therapeutic Interventions ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Low Grade ◽  
Endothelium Dysfunction ◽  
Age Related

Abstract The continued increase in global life expectancy predicts a rising prevalence of age-related cerebral small vessel diseases (CSVD), which requires a better understanding of the underlying molecular mechanisms. In recent years, the concept of “inflammaging” has attracted increasing attention. It refers to the chronic sterile low-grade inflammation in elderly organisms and is involved in the development of a variety of age-related chronic diseases. Inflammaging is a long-term result of chronic physiological stimulation of the immune system, and various cellular and molecular mechanisms (e.g., cellular senescence, immunosenescence, mitochondrial dysfunction, defective autophagy, metaflammation, gut microbiota dysbiosis) are involved. With the deepening understanding of the etiological basis of age-related CSVD, inflammaging is considered to play an important role in its occurrence and development. One of the most critical pathophysiological mechanisms of CSVD is endothelium dysfunction and subsequent blood-brain barrier (BBB) leakage, which gives a clue in the identification of the disease by detecting circulating biological markers of BBB disruption. The regional analysis showed blood markers of vascular inflammation are often associated with deep perforating arteriopathy (DPA), while blood markers of systemic inflammation appear to be associated with cerebral amyloid angiopathy (CAA). Here, we discuss recent findings in the pathophysiology of inflammaging and their effects on the development of age-related CSVD. Furthermore, we speculate the inflammaging as a potential target for future therapeutic interventions to delay or prevent the progression of the age-related CSVD.

scholarly journals Adipokines and Inflammation: Focus on Cardiovascular Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7711 ◽  
Author(s):  
Sandra Feijóo-Bandín ◽  
Alana Aragón-Herrera ◽  
Sandra Moraña-Fernández ◽  
Laura Anido-Varela ◽  
Estefanía Tarazón ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Low Grade ◽  
Bioactive Substances ◽  
Endocrine Organ ◽  
Adipose Tissue Dysfunction ◽  
Inflammatory Processes ◽  
Regulatory Functions

It is well established that adipose tissue, apart from its energy storage function, acts as an endocrine organ that produces and secretes a number of bioactive substances, including hormones commonly known as adipokines. Obesity is a major risk factor for the development of cardiovascular diseases, mainly due to a low grade of inflammation and the excessive fat accumulation produced in this state. The adipose tissue dysfunction in obesity leads to an aberrant release of adipokines, some of them with direct cardiovascular and inflammatory regulatory functions. Inflammation is a common link between obesity and cardiovascular diseases, so this review will summarise the role of the main adipokines implicated in the regulation of the inflammatory processes occurring under the scenario of cardiovascular diseases.

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.

scholarly journals The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results

2021 ◽  
Vol 22 (18) ◽  
pp. 10152
Author(s):  
Roland Gal ◽  
Laszlo Deres ◽  
Kalman Toth ◽  
Robert Halmosi ◽  
Tamas Habon
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Causes Of Death ◽  
Antioxidant Properties ◽  
Clinical Results ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Cardioprotective Effects ◽  
Anti Inflammatory

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases and their risk factors. The aim of this review was to summarize the wide beneficial effects of resveratrol on the cardiovascular system, including signal transduction pathways of cell longevity, energy metabolism of cardiomyocytes or cardiac remodeling, and its anti-inflammatory and antioxidant properties. In addition, this paper discusses the significant preclinical and human clinical trials of recent years with resveratrol on cardiovascular system. Finally, we present a short overview of antiviral and anti-inflammatory properties and possible future perspectives on RES against COVID-19 in cardiovascular diseases.

scholarly journals Coronary Microvascular Dysfunction

2021 ◽  
Author(s):  
Shigeo Godo ◽  
Akira Suda ◽  
Jun Takahashi ◽  
Satoshi Yasuda ◽  
Hiroaki Shimokawa
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Microvascular Dysfunction ◽  
Therapeutic Interventions ◽  
Coronary Microvascular Dysfunction ◽  
Clinical Settings ◽  
Structural Factors ◽  
The Past ◽  
Microvascular Resistance ◽  
Insight Into

Over the past couple of decades, accumulating evidence has shown that structural and functional abnormalities of coronary microvasculature are highly prevalent, associated with adverse clinical outcomes in patients with various cardiovascular diseases. The term coronary microvascular dysfunction (CMD) has been coined to refer to this clinical condition and is increasingly recognized as an important clinical entity in many clinical settings. The potential mechanisms of CMD appear to be heterogenous, including enhanced coronary vasoconstrictive reactivity at microvascular level, impaired endothelium-dependent and independent coronary vasodilator capacities, and increased coronary microvascular resistance secondary to structural factors. Recent experimental and clinical studies have highlighted emerging modulators of vascular functions, vital insight into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will briefly review the current progress on pathophysiology, molecular mechanisms, and clinical management of CMD from bench to bedside.

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