scholarly journals The Emerging Role of TLR and Innate Immunity in Cardiovascular Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Rolf Spirig ◽  
Janice Tsui ◽  
Sidney Shaw
Keyword(s):  
Cardiovascular Disease ◽  
Innate Immunity ◽  
Immune System ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Microvascular Complications ◽  
Cell Types ◽  
Current Evidence

Cardiovascular disease is a complex disorder involving multiple pathophysiological processes, several of which involve activation of toll-like receptors (TLRs) of the innate immune system. As sentinels of innate immunity TLRs are nonclonally germline-encoded molecular pattern recognition receptors that recognize exogenous as well as tissue-derived molecular dangers signals promoting inflammation. In addition to their expression in immune cells, TLRs are found in other tissues and cell types including cardiomyocytes, endothelial and vascular smooth muscle cells. TLRs are differentially regulated in various cell types by several cardiovascular risk factors such as hypercholesterolemia, hyperlipidemia, and hyperglycemia and may represent a key mechanism linking chronic inflammation, cardiovascular disease progression, and activation of the immune system. Modulation of TLR signaling by specific TLR agonists or antagonists, alone or in combination, may be a useful therapeutic approach to treat various cardiovascular inflammatory conditions such as atherosclerosis, peripheral arterial disease, secondary microvascular complications of diabetes, autoimmune disease, and ischemia reperfusion injury. In this paper we discuss recent developments and current evidence for the role of TLR in cardiovascular disease as well as the therapeutic potential of various compounds on inhibition of TLR-mediated inflammatory responses.

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 The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4370
Author(s):  
Cássia de Fáveri ◽  
Paula M. Poeta Fermino ◽  
Anna P. Piovezan ◽  
Lia K. Volpato
Keyword(s):  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Integrative Review ◽  
Inflammatory Factors ◽  
Resolvin D1 ◽  
Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential

2010 ◽  
Vol 120 (6) ◽  
pp. 219-229 ◽  
Author(s):  
Madhav Lavu ◽  
Shashi Bhushan ◽  
David J. Lefer
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Hydrogen Sulfide ◽  
Therapeutic Potential ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Signalling Molecule ◽  
Anti Inflammatory ◽  
Antioxidant Effects

H2S (hydrogen sulfide), viewed with dread for more than 300 years, is rapidly becoming a ubiquitously present and physiologically relevant signalling molecule. Knowledge of the production and metabolism of H2S has spurred interest in delineating its functions both in physiology and pathophysiology of disease. Although its role in blood pressure regulation and interaction with NO is controversial, H2S, through its anti-apoptotic, anti-inflammatory and antioxidant effects, has demonstrated significant cardioprotection. As a result, a number of sulfide-donor drugs, including garlic-derived polysulfides, are currently being designed and investigated for the treatment of cardiovascular conditions, specifically myocardial ischaemic disease. However, huge gaps remain in our knowledge about this gasotransmitter. Only by additional studies will we understand more about the role of this intriguing molecule in the treatment of cardiovascular disease.

scholarly journals ON VASCULAR STENOSIS, RESTENOSIS AND MANNOSE BINDING LECTIN

2016 ◽  
Vol 29 (1) ◽  
pp. 57-59 ◽  
Author(s):  
Barbara Stadler KAHLOW ◽  
Rodrigo Araldi NERY ◽  
Thelma L SKARE ◽  
Carmen Australia Paredes Marcondes RIBAS ◽  
Gabriela Piovezani Ramos ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mannose Binding Lectin ◽  
Mannose Binding ◽  
Vascular Stenosis ◽  
Micro Organisms ◽  
The Complement System ◽  
Binding Lectin

Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.

scholarly journals The Cardioprotective Effects of Hydrogen Sulfide in Heart Diseases: From Molecular Mechanisms to Therapeutic Potential

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yaqi Shen ◽  
Zhuqing Shen ◽  
Shanshan Luo ◽  
Wei Guo ◽  
Yi Zhun Zhu
Keyword(s):  
Hydrogen Sulfide ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Cardiac Diseases ◽  
Mammalian Tissues ◽  
Antioxidative Action

Hydrogen sulfide (H2S) is now recognized as a third gaseous mediator along with nitric oxide (NO) and carbon monoxide (CO), though it was originally considered as a malodorous and toxic gas. H2S is produced endogenously from cysteine by three enzymes in mammalian tissues. An increasing body of evidence suggests the involvement of H2S in different physiological and pathological processes. Recent studies have shown that H2S has the potential to protect the heart against myocardial infarction, arrhythmia, hypertrophy, fibrosis, ischemia-reperfusion injury, and heart failure. Some mechanisms, such as antioxidative action, preservation of mitochondrial function, reduction of apoptosis, anti-inflammatory responses, angiogenic actions, regulation of ion channel, and interaction with NO, could be responsible for the cardioprotective effect of H2S. Although several mechanisms have been identified, there is a need for further research to identify the specific molecular mechanism of cardioprotection in different cardiac diseases. Therefore, insight into the molecular mechanisms underlying H2S action in the heart may promote the understanding of pathophysiology of cardiac diseases and lead to new therapeutic targets based on modulation of H2S production.

scholarly journals Secretome Profiling of Atlantic Salmon Head Kidney Leukocytes Highlights the Role of Phagocytes in the Immune Response to Soluble β-Glucan

2021 ◽  
Vol 12 ◽  
Author(s):  
Dimitar B. Iliev ◽  
Guro Strandskog ◽  
Mehrdad Sobhkhez ◽  
Jack A. Bruun ◽  
Jorunn B. Jørgensen
Keyword(s):  
Immune System ◽  
Atlantic Salmon ◽  
Primary Cultures ◽  
Head Kidney ◽  
Cell Types ◽  
Mononuclear Phagocytes ◽  
Immunostimulatory Activity ◽  
Complement Receptor 3 ◽  
Bacteria And Fungi

β‐Glucans (BG) are glucose polymers which are produced in bacteria and fungi but not in vertebrate organisms. Being recognized by phagocytic leukocytes including macrophages and neutrophils through receptors such as dectin-1 and Complement receptor 3 (CR3), the BG are perceived by the innate immune system of vertebrates as foreign substances known as Pathogen Associated Molecular Patterns (PAMPs). The yeast-derived BG has been recognized for its potent biological activity and it is used as an immunomodulator in human and veterinary medicine. The goal of the current study was to characterize the immunostimulatory activity of soluble yeast BG in primary cultures of Atlantic salmon (Salmo salar) head kidney leukocytes (HKLs) in which phagocytic cell types including neutrophils and mononuclear phagocytes predominate. The effect of BG on the secretome of HKL cultures, including secretion of extracellular vesicles (EVs) and soluble protein55s was characterized through western blotting and mass spectrometry. The results demonstrate that, along with upregulation of proinflammatory genes, BG induces secretion of ubiquitinated proteins (UbP), MHCII-containing EVs from professional antigen presenting cells as well as proteins derived from granules of polymorphonuclear granulocytes (PMN). Among the most abundant proteins identified in BG-induced EVs were beta-2 integrin subunits, including CD18 and CD11 homologs, which highlights the role of salmon granulocytes and mononuclear phagocytes in the response to soluble BG. Overall, the current work advances the knowledge about the immunostimulatory activity of yeast BG on the salmon immune system by shedding light on the effect of this PAMP on the secretome of salmon leukocytes.

scholarly journals The Effect of Air Pollution on the Immune System

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Diana Liu
Keyword(s):  
Cardiovascular Disease ◽  
Air Pollution ◽  
Innate Immunity ◽  
Particulate Matter ◽  
Immune System ◽  
Sulfur Dioxide ◽  
Nitrogen Oxide ◽  
Immune Cells ◽  
Cytokine Secretion ◽  
Acquired Immunity

Air pollution has become a serious problem, the pollutant mainly came from industrial and vehicle exhaustion will harm people’s bodies to a different extent, cause lots of diseases like asthma, and cardiovascular disease. The system protects us are also be damaged by pollutant entering the tissue barrier, harm to immune cells and regulate cytokine secretion. This essay is mainly focused on the particulate matter, sulfur dioxide, and nitrogen oxide effect on the immune system from the innate immunity to the acquired immunity, and how the immune system defense.

The probiotic supplementation role in improving the immune system among people with ulcerative colitis: a narrative review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Lana M. Agraib ◽  
Mohammed I. Yamani ◽  
Yaser Mohammed Rayyan ◽  
Awni Taleb Abu-Sneineh ◽  
Tarek A. Tamimi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immune System ◽  
Inflammatory Responses ◽  
Narrative Review ◽  
Mucosal Barrier ◽  
Current Evidence ◽  
Chronic Inflammatory Bowel Disease ◽  
Inflammatory Factor ◽  
Therapeutic Benefits ◽  
Mucosal Barrier Function

Abstract Objectives The purpose of this paper is to summarize the current evidence on probiotics’ uses as an adjuvant for ulcerative colitis (UC) and provide an understanding of the effect of probiotics supplement on the immune system and inflammatory responses among UC patients and subsequent therapeutic benefits. Content A narrative review of all the relevant published papers known to the author was conducted. Summary UC is a chronic inflammatory bowel disease (IBD) that results in inflammation and ulceration of the colon and rectum. The primary symptoms of active disease are diarrhea, abdominal pain, and rectal bleeding. About 70% of the human immune system (mucosal-associated lymphoid tissue) originates in the intestine. Probiotics are live microorganisms that help in stabilizing the gut microbiota (nonimmunologic gut defense), restores normal flora, and enhance the humoral immune system. Probiotics especially Bifidobacterium, Saccharomyces boulardii, and lactic acid-producing bacteria have been used as an adjunct therapy for treating UC to ameliorate disease-related symptoms and reduce relapse rate. Probiotics, in general, modulate the immune system through their ability to enhance the mucosal barrier function, or through their interaction with the local immune system to enhance regulatory T cell responses, decrease the pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin 1 beta and increase anti-inflammatory factor interleukin 10. Outlook More studies are needed to explore the properties of the various probiotic bacterial strains, their different uses, as well as the dosage of probiotics and duration for treating different disorders. Further clinical investigations on mechanisms of action and how probiotics modulate the immune system may lead to further advances in managing IBD.

Abstract 316: Role of an Inflammasome Adaptor Molecule ASC (Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain) in Myocardial Ischemia-Reperfusion Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masanori Kawaguchi ◽  
Masafumi Takahashi ◽  
Takeki Hata ◽  
Yasuko Takahashi ◽  
Hajime Morimoto ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Caspase Recruitment Domain ◽  
Lv Dysfunction ◽  
Infarct Area ◽  
Injured Myocardium ◽  
Myocardial Ischemia Reperfusion

Inflammatory responses play a key role in the pathophysiology of myocardial ischemia-reperfusion (I/R) injury. ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) is an adaptor protein that forms “inflammasome” whose activation leads to caspase-1-dependent interleukin (IL)-1β generation and subsequent inflammatory responses; however, the role of ASC in myocardial I/R injury remains unclear. Baseline left ventricular (LV) function was unaltered in ASC-deficient (ASC −/− ) mice. ASC −/− (n=42) and wild-type control (WT) (n=42) mice were subjected to 30 min LAD occlusion, followed by reperfusion. ASC −/− mice showed reduced infarct area (infarct area/area at risk: 18.7% vs. 28.6% at 48 h, p< 0.01) and scar formation (scar/LV area: 9.7% vs. 14.6% at 14 days, p< 0.01) after myocardial I/R. Echocardiography showed improved LV dysfunction (%FS: 35.2 vs. 28.4 at 7 days, p< 0.01; 34.0 vs. 25.7 at 14 days, p< 0.01) and dimensions (LVEDD [mm]: 3.88 vs. 4.21 at 7 days, p< 0.01; 3.99 vs. 4.43 at 14 days, p< 0.01) in the ASC −/− mice after myocardial I/R. Immunohistochemistry revealed that infiltration of macrophages (Mac3) and neutrophils (Gr-1) was markedly decreased in the injured myocardium of the ASC −/− mice (48 hr [/mm 2 ]: 1226 vs. 884, p< 0.01; 782 vs. 554, p< 0.01, respectively); however, there was no difference of neovascularization (CD31) in the ischemic area. Double immunofluorescent staining showed that ASC expression was clearly observed in the infiltrated macrophages and neutrophils in the injured myocardium. Real-time RT-PCR analysis demonstrated that the myocardial expression of inflammatory cytokines, such as IL-1β, IL-6, and MCP-1, after I/R were significantly decreased in the ASC −/− mice, compared to that in the WT mice. Further, in vitro experiments showed that LPS-induced production of these inflammatory cytokines in the ASC −/− bone marrow cells was significantly decreased. These findings demonstrate that ASC deficiency prevents inflammatory cell infiltration and cytokine expression, thereby resulting in the improvement of LV dysfunction and remodeling after myocardial I/R injury, and suggest that ASC is a novel therapeutic target for myocardial I/R injury.

Infection and immunity

2021 ◽  
pp. 853-920
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Cell Types ◽  
The Body ◽  
Acquired Immunity ◽  
Histocompatibility Complex ◽  
Repair Mechanisms ◽  
Antigen Presenting ◽  
Different Cell Types

‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).

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