scholarly journals The Innate Immune cGAS-STING-Pathway in Cardiovascular Diseases – A Mini Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Lavinia Rech ◽  
Peter P. Rainer
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Cyclic Gmp ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Dna Sensor ◽  
Sting Pathway

Inflammation plays a central role in cardiovascular diseases (CVD). One pathway under investigation is the innate immune DNA sensor cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING). cGAS-STING upregulates type I interferons in response to pathogens. Recent studies show that also self-DNA may activate cGAS-STING, for instance, DNA released from nuclei or mitochondria during obesity or myocardial infarction. Here, we focus on emerging evidence describing the interaction of cGAS-STING with cardiovascular risk factors and disease. We also touch on translational therapeutic opportunities and potential further investigations.

CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION AND CHRONIC INFLAMMATORY LUNG DISEASES

2020 ◽  
pp. 21-25
Author(s):  
Tupitsyn V.V. ◽  
Bataev Kh.M. ◽  
Men’shikova A.N. ◽  
Godina Z.N.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Digestive System ◽  
Control Group ◽  
Study Group ◽  
Type I ◽  
Internal Organs ◽  
History Of

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.

scholarly journals Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 675
Author(s):  
Samira Elmanfi ◽  
Mustafa Yilmaz ◽  
Wilson W. S. Ong ◽  
Kofi S. Yeboah ◽  
Herman O. Sintim ◽  
...  
Keyword(s):  
Immune Response ◽  
Periodontal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Vaccine Adjuvants ◽  
Cyclic Dinucleotides ◽  
Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

scholarly journals Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells

Reproduction ◽  
2017 ◽  
Vol 153 (6) ◽  
pp. 821-834 ◽  
Author(s):  
Keqin Yan ◽  
Dingqing Feng ◽  
Jing Liang ◽  
Qing Wang ◽  
Lin Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Granulosa Cells ◽  
Innate Immune ◽  
Type I Interferons ◽  
Endocrine Function ◽  
Type I ◽  
Dna Sensor ◽  
Innate Immune Responses ◽  
Oligoadenylate Synthetase ◽  
Ovarian Granulosa Cells

Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analog, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation respectively. Moreover, several IFN-inducible antiviral proteins, including 2′,5′-oligoadenylate synthetase, IFN-stimulating gene 15 and Mx GTPase 1, were also induced by VACV70 transfection. The innate immune responses in granulosa cells were significantly reduced by the transfection of specific small-interfering RNAs targeting p204, cGas or Sting. Notably, the VACV70-triggered innate immune responses affected steroidogenesis in vivo and in vitro. The data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.

scholarly journals How the Innate Immune DNA Sensing cGAS–STING Pathway Is Involved in Autophagy

2021 ◽  
Vol 22 (24) ◽  
pp. 13232
Author(s):  
Wanglong Zheng ◽  
Nengwen Xia ◽  
Jiajia Zhang ◽  
Nanhua Chen ◽  
François Meurens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Responses ◽  
Complex Interaction ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Innate Immune Responses ◽  
Homeostatic Process ◽  
Sting Pathway ◽  
Dna Complex

The cGAS–STING pathway is a key component of the innate immune system and exerts crucial roles in the detection of cytosolic DNA and invading pathogens. Accumulating evidence suggests that the intrinsic cGAS–STING pathway not only facilitates the production of type I interferons (IFN-I) and inflammatory responses but also triggers autophagy. Autophagy is a homeostatic process that exerts multiple effects on innate immunity. However, systematic evidence linking the cGAS–STING pathway and autophagy is still lacking. Therefore, one goal of this review is to summarize the known mechanisms of autophagy induced by the cGAS–STING pathway and their consequences. The cGAS–STING pathway can trigger canonical autophagy through liquid-phase separation of the cGAS–DNA complex, interaction of cGAS and Beclin-1, and STING-triggered ER stress–mTOR signaling. Furthermore, both cGAS and STING can induce non-canonical autophagy via LC3-interacting regions and binding with LC3. Subsequently, autophagy induced by the cGAS–STING pathway plays crucial roles in balancing innate immune responses, maintaining intracellular environmental homeostasis, alleviating liver injury, and limiting tumor growth and transformation.

scholarly journals Features of the structure of cardiovascular diseases risk factors for complicated myocardial rupture myocardial infarction in young and middle-aged men

2021 ◽  
Vol 40 (2) ◽  
pp. 49-54
Author(s):  
Al’farabi S. Izmuhanov ◽  
Aleksandr V. Gordienko
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Risk Groups ◽  
Control Group ◽  
Study Group ◽  
Type I ◽  
Increased Risk ◽  
Myocardial Rupture

AIM: Myocardial rupture currently remains in most cases a fatal complication of myocardial infarction. OBJECTIVE: To study the features of the structure of cardiovascular risk factors in men under 60 years old with complicated myocardial infarction to improve prevention. MATERIALS AND METHODS: The study included men 1960 years old with type I myocardial infarction. The patients were divided into two groups age-comparable: I studied, with myocardial rupture seven patients; II control, without breaks 558 patients. A comparative analysis of the frequency of observation of the main and additional factors of cardiovascular risk in the selected groups was performed. RESULTS OF THE STUDY: In the patients of the study group, frequent (four or more times a year) colds were observed more often than in the control group (42.9 and 14.8%, respectively; p = 0.04), the internal organs foci of infections (85.7 and 40.3%; p = 0.049), bypass surgery (57.1 and 10.2%; p 0.0001) and continuous cardiac pacing (28.6 and 0.5%; p 0.0001) in medical history. The presence of arterial hypertension (28.5 and 67.6%; p = 0.03) and foci of oral cavity infections (0 and 20.3%; p = 0.049) reduced the risk of myocardial rupture. In the study group, the levels of total cholesterol (4.3 0.3 and 5.8 1.2 mmol/l); p = 0.02), low-density lipoproteins (2.7 0.1 and 4.2 1.2 mmol/l); p = 0.04) and triglycerides (0.7 0.1 and 2.6 1.8 mmol/l); p = 0.008) were lower than in the control. CONCLUSION: Combinations of these cardiovascular risk factors indicate an increased risk of myocardial rupture. It is advisable to use them for predictive modeling of this event and the formation of risk groups for the purpose of timely prevention, (bibliography: 18 refs.).

scholarly journals CONTROL OF CARDIOVASCULAR RISK FACTORS IN PATIENTS AFTER MYOCARDIAL INFARCTION

2019 ◽  
Vol 72 (3) ◽  
pp. 472-483
Author(s):  
Jan W. Pęksa ◽  
Piotr Jankowski ◽  
Danuta Czarnecka
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Antiplatelet Therapy ◽  
Cardiovascular Prevention ◽  
Pharmacological Therapy ◽  
Unhealthy Lifestyle ◽  
Individual Level ◽  
Coronary Syndrome

Despite significant improvements in the diagnosis and treatment of cardiovascular diseases that have occurred in recent years, they remain the main cause of morbidity and mortality in the population. In many European countries, the incidence of coronary heart disease is currently 50% lower than it was in the early 1980s, which is the result of cardiovascular prevention. A special group of patients are people after myocardial infarction with very high cardiovascular risk. They should definitely implement activities at the individual level e. g. work on improving the unhealthy lifestyle and pharmacologically control other risk factors. A diet low in saturated fats should be recommended, i.e. mainly containing whole grains, vegetables, fruits and fish, recommend regular physical exercise: 150 min / week of moderate, aerobic physical activity, reducing the supply of calories in order to get rid of overweight or obesity. Help in quitting tobacco addiction should take place through the minimal nicotine intervention and, if necessary, pharmacological therapy. Another thing is the control of other risk factors, i. e. the appropriate treatment of dyslipidemia (the primary target is LDL cholesterol <1.8 mmol/l or reduction by ≥ 50%, if the initial concentration is between 1.8 and 3.5 mmol/l, treatment hypertension (target arterial pressure for most people aged 18–65 is in the range: 120–130/70–79 mmHg, if it is well tolerated, while for older people it is in the range: 130–139/70–79mmHg, if it is well tolerated), optimal diabetes therapy (target glycated hemoglobin <7%) and appropriate antiplatelet therapy (in most patients double antiplatelet therapy is recommended for 12 months after acute coronary syndrome). These activities lead to a significant improvement in quality of life and a decrease in mortality due to cardiovascular diseases.

CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 50 YEARS OLD WITH MYOCARDIAL INFARCTION, COMPLICATED CARDIOGENIC SHOCK

2021 ◽  
pp. 234-240
Author(s):  
Gordienko A.V. ◽  
Balabanov A.S. ◽  
Biyaliev E.K.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiogenic Shock ◽  
Cardiovascular Risk Factors ◽  
High Density Lipoproteins ◽  
Control Group ◽  
Study Group ◽  
Type I ◽  
Low Density

Relevance. Mortality in cardiogenic shock remains high. Aim. To evaluate the structure of cardiovascular risk factors features in men under 50 years old with myocardial infarction complicated by cardiogenic shock, in order to improve the prevention of this complication. Material and methods. The study included men 19-50 years old with type I myocardial infarction. The patients were divided into two age-comparable groups: I - the study group, with cardiogenic shock - seven patients; II - control, without it - 202 patients. A comparative analysis of the of cardiovascular risk factors structure in the selected groups and a risk analysis (ANOVA) of the development of cardiogenic shock were performed. Results. In the study group, the predominance of renal dysfunction (100 and 10.3%, respectively; p=0.004), alcohol abuse (71.4 and 35.2%; p=0.049), the presence of atrial fibrillation (57.1 and 5,0%; p˂0.0001), urolithiasis 28.6 and 6.4%; p=0.001), cholelithiasis 14.3 and 5.5%; p=0.001 and gout 14.3 and 0.5%; p=0.001) in history. In the control group, a history of unstable angina pectoris was more often recorded (0 and 38.1%; p=0.04). When assessing the risks, in addition to those listed, smoking 20 cigarettes per day, a decrease in lipid metabolism indicators (very low density lipoproteins 0.36 mmol/l, low density 2.7 mmol/l, cholesterol˂3,8 mmol/l, triglycerides 1.2 mmol/l, cholesterol/high density lipoproteins˂4.63), creatinine≥140 μmol/l in combination with overweight (≥96.0 kg and Quetelet index ≥31,0 kg/m2) and age (≥48 years). Conclusions. The listed factors can be used in the formation of high-risk groups for observation and timely implementation of the necessary treatment as well as for prognostic modeling of cardiogenic shock.

scholarly journals ABCC1/MRP1 exports cGAMP and modulates cGAS-dependent immunity

2021 ◽  
Author(s):  
Joanna H. Maltbaek ◽  
Jessica M. Snyder ◽  
Daniel B. Stetson
Keyword(s):  
Mouse Model ◽  
Cyclic Gmp ◽  
Regulatory Mechanism ◽  
Type I Interferon ◽  
Type I ◽  
Adapter Protein ◽  
Dna Sensor ◽  
Interferon Production ◽  
Sting Pathway ◽  
Cyclic Dinucleotide

AbstractThe DNA sensor cyclic GMP-AMP synthase (cGAS) is important for antiviral and anti-tumor immunity. cGAS generates cyclic GMP-AMP (cGAMP), a diffusible cyclic dinucleotide that activates the antiviral response through the adapter protein Stimulator of Interferon Genes (STING). cGAMP is negatively charged and cannot passively cross cell membranes, but recent advances have established a role for extracellular cGAMP as an “immunotransmitter” that can be imported into cells. However, the mechanism by which cGAMP exits cells remains unknown. Here, we identify ABCC1/MRP1 as an ATP-dependent cGAMP exporter that influences STING signaling and type I interferon production. We demonstrate that ABCC1 deficiency exacerbates cGAS-dependent autoimmunity in the Trex1-/- mouse model of Aicardi-Goutières syndrome. These studies identify ABCC1-mediated cGAMP export as a key regulatory mechanism of the cGAS-STING pathway.

TO THE QUESTION OF THE CARDIOVASCULAR RISK FACTORS IN MEN UNDER 50 YEARS OLD WITH MYOCARDIAL INFARCTION AND ARTERIAL HYPERTENSION

2021 ◽  
pp. 254-260
Author(s):  
Gordienko A.V. ◽  
Davletova A.K.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Arterial Hypertension ◽  
Cardiovascular Risk Factors ◽  
Target Organ Damage ◽  
Vascular Pathology ◽  
Control Group ◽  
Type I ◽  
The Third

Relevance. Myocardial infarction and its complications in young and middle-aged men with arterial hypertension remains an important problem of modern cardiology. Aim. To evaluate the cardiovascular risk factors structure features in men under 50 years old with arterial hypertension to improve prevention and outcomes. Material and methods. The study included 209 men aged 19-50 years old with type I myocardial infarction, who underwent a standard diagnostic algorithm in the first 48 hours and at the end of the third week of the disease. The patients were divided into two age-matched groups: with arterial hypertension (121 patients, 88 patients without arterial hypertension). A comparative analysis of the frequency of identifying the main and additional cardiovascular risk factors and their parameters were performed in the selected groups. Results. The study group showed more pronounced glycemia (5.6±1.4 mmol/l) than in the control group (5.2±1.3 mmol/l; p=0.04) at the end of the third week of myocardial infarction. In this group, there was a high incidence of obesity (42.1 and 25.0%, respectively; p=0.01), changes in peripheral arteries (86.0 and 3.5%; p<0.0001) and target organ damage , meteorological dependence (31.4 and 9.1%; p=0.0001), impaired peripheral hemodynamics, as well as hereditary burden of vascular pathology (100 and 56.8%; p=0.03). Conclusions. The data obtained suggest a worse long-term prognosis and a greater degree of resistance to treatment in men with arterial hypertension, which must be considered when implementing preventive programs.

CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH RECURRENT ISCHAEMIC DAMAGES DURING MYOCARDIAL INFARCTION

2020 ◽  
pp. 16-20
Author(s):  
Epifanov S.Y. ◽  
Tupitsyn V.V. ◽  
Baltabaeva A.M.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Coronary Artery Bypass Surgery ◽  
Artery Bypass ◽  
Risk Groups ◽  
Control Group ◽  
Study Group ◽  
Type I

Relevance. Recurrent ischemic damages negatively affect the prognosis of myocardial infarction. Aim. To evaluate the peculiarities of cardiovascular risk factors in men younger than 60 years old with myocardial infarction and recurrent ischemic damages to improve prevention, and outcomes. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with recurrent ischemic damages - 95 patients; II - con-trol, without it - 470 patients. A comparative analysis of the frequency of observation of the main and additional car-diovascular risk factors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hypodynamia (94.7 and 77.7%, respectively; p ˂ 0.05), smoking (86.3 and 72.6%; p ˂ 0.05), myocardial infarction (56.8 and 40.3%; p ˂ 0.05), unstable angina (57.9 and 46.3%; p ˂ 0.05), coronary artery bypass surgery (17.9 and 9, 3%; p ˂ 0.05) in the pa-tient’s medical a history, stress (53.7 and 36.9%; p ˂ 0.05) and changes in meteorological factors (26.4 and 23.0%; p ˂ 0.05) as causes of myocardial infarction , winter (37.9 and 28.1%; p ˂ 0.05) and autumn (28.4 and 18.3%; p ˂ 0.05) periods and impaired renal function (29.2 and 12.1% ; p ˂ 0.05). Conclusions. The use of these factors in prognostic modeling of recurring ischemic damages risk in case of myocardi-al infarction in men under 60 years old, as well as in creating high-risk groups for their development to monitor and conduct preventive measures, will improve the outcome of such patients.

Sign in / Sign up

Export Citation Format

Share Document