Anti-inflammatory Strategies in Atherosclerosis

2021 ◽  
Vol 41 (06) ◽  
pp. 433-442
Author(s):  
Heiko Bugger ◽  
Andreas Zirlik
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Inflammatory Disease ◽  
Vascular Inflammation ◽  
Chronic Inflammatory Disease ◽  
Atherosclerotic Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Atherosclerotic Vascular Disease ◽  
Risk Factor Management ◽  
Anti Inflammatory

AbstractAtherosclerotic vascular disease and its related complications are the major cause of mortality in Western societies. Atherosclerosis is a chronic inflammatory disease of the arterial wall triggered by traditional and nontraditional risk factors and mediated by inflammatory and immune responses. Recent clinical trials provided compelling evidence corroborating that atherosclerosis is an inflammatory disease and demonstrated efficacy of anti-inflammatory interventions in reducing cardiovascular events and mortality. Traditional risk factors drive vascular inflammation, further justifying the instrumental role of intensified risk factor management in attenuating and preventing atherosclerotic disease and complications. Promising therapeutic approaches specifically related to inhibition of inflammation span traditional anti-inflammatory drugs, specific immunomodulation, and development of vaccination against atherosclerotic disease. Here, we review the inflammatory component in atherogenesis, the available evidence from clinical trials evaluating efficacy of therapeutic anti-inflammatory interventions in patients with high cardiovascular risk, and discuss potential future targets for anti-inflammatory or immune modulatory treatment in atherosclerotic cardiovascular disease.

scholarly journals Extra-articular rheumatoid arthritis

Reumatismo ◽  
2018 ◽  
Vol 70 (4) ◽  
pp. 212-224 ◽  
Author(s):  
E. Marcucci ◽  
E. Bartoloni ◽  
A. Alunno ◽  
M.C. Leone ◽  
G. Cafaro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
General Practitioners ◽  
Inflammatory Disease ◽  
Health Professionals ◽  
Cardiovascular Events ◽  
Chronic Inflammatory Disease ◽  
Rheumatoid Nodules

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints, though a consistent proportion of patients may also display extra articular manifestations (EAMs). From rheumatoid nodules to interstitial lung disease, from cardiovascular events to vasculitis, the spectrum of EAMs encompasses various conditions with different prognoses. EAMs may also occur as first RA manifestation, therefore the coordination with other health professionals, including general practitioners, is needed. The aim of this article is to provide an overview on EAMs in RA with particular focus on the recognised risk factors and the available recommendations for managing them, as well as comorbidities in RA patients.

Engineering activated protein C to maximize therapeutic efficacy

2015 ◽  
Vol 43 (4) ◽  
pp. 691-695 ◽  
Author(s):  
Louise M. Quinn ◽  
Clive Drakeford ◽  
James S. O’Donnell ◽  
Roger J.S. Preston
Keyword(s):  
Clinical Trials ◽  
Protein Engineering ◽  
Inflammatory Disease ◽  
Therapeutic Efficacy ◽  
Protein C ◽  
Thrombus Formation ◽  
Activated Protein C ◽  
Bleeding Risk ◽  
Protective Role ◽  
Chronic Inflammatory Disease

The anticoagulant-activated protein C (APC) acts not solely as a crucial regulator of thrombus formation following vascular injury, but also as a potent signalling enzyme with important functions in the control of both acute and chronic inflammatory disease. These properties have been exploited to therapeutic effect in diverse animal models of inflammatory disease, wherein recombinant APC administration has proven to effectively limit disease progression. Subsequent clinical trials led to the use of recombinant APC (Xigris) for the treatment of severe sepsis. Although originally deemed successful, Xigris was ultimately withdrawn due to lack of efficacy and an unacceptable bleeding risk. Despite this apparent failure, the problems that beset Xigris usage may be tractable using protein engineering approaches. In this review, we detail the protein engineering approaches that have been utilized to improve the therapeutic characteristics of recombinant APC, from early studies in which the distinct anti-coagulant and signalling activities of APC were separated to reduce bleeding risk, to current attempts to enhance APC cytoprotective signalling output for increased therapeutic efficacy at lower APC dosage. These novel engineered variants represent the next stage in the development of safer, more efficacious APC therapy in disease settings in which APC plays a protective role.

Millet shell polyphenols prevent atherosclerosis by protecting gut barrier and remodeling gut microbiota in ApoE-/- mice

2021 ◽  
Author(s):  
Fengming Liu ◽  
Shuhua Shan ◽  
Hanqing Li ◽  
Jiangying Shi ◽  
Ruilin Hao ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Gut Microbiota ◽  
Inflammatory Disease ◽  
Chronic Inflammatory Disease ◽  
Gut Barrier ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease. The anti-inflammatory effect of certain polyphenols have been recognized. Active polyphenols were extracted from millet shell (MSP)，and the...

21: DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI: FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE INITIATIVE

2016 ◽  
Vol 64 (3) ◽  
pp. 815.2-816
Author(s):  
MT Kabbany ◽  
AA Joshi ◽  
M Ahlman ◽  
J Rodante ◽  
JB Lerman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Fdg Pet ◽  
Particle Concentration ◽  
Vascular Inflammation ◽  
Chronic Inflammatory Disease ◽  
Human Model ◽  
Cardiometabolic Disease ◽  
Model Assessment ◽  
Mri Findings

Purpose of StudyPsoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a clinical human model to study inflammatory atherogenesis. We aimed to assess the major determinants of vascular inflammation (VI) measured by 18FDG PET-MRI in a well-phenotyped PSO cohort.Methods Used124 consecutive patients with PSO underwent 18FDG PET-MRI scans. We used target-to-background ratio to quantify VI 120 minutes post FDG injection. Homeostatic model assessment of insulin resistance (HOMA-IR) was measured, along with cholesterol efflux capacity (CEC) and HDL particle concentration by NMR (Liposcience) fasting.Summary of ResultsOur cohort was middle aged (mean 49±13.3 years) with mild to moderate PSO, and low CV risk (median Framingham Risk Score (FRS) 2, IQR 2–6). PSO was associated with increased VI (β=0.27, p<0.005), compared to healthy controls. VI was associated with HOMA-IR (β=0.26, p<0.001), CEC (β=−0.12, p=0.04) and HDL particle concentration (β=−0.19, p=0.003) beyond traditional CV risk factors (age, gender, FRS and BMI). Among these, HOMA-IR provided maximum incremental value in predicting VI beyond traditional risk factors (χ2=39.36, p<0.001).ConclusionsVI by FDG PET MRI is associated with traditional CV risk factors and cardiometabolic parameters. Insulin resistance and CEC were most strongly associated with VI by 18FDG PET-MRI beyond traditional CV risk factors and BMI in PSO suggesting that cardiometabolic disease increases CV risk in PSO.Abstract 21 Figure 1

Relevance and potential of sphingosine-1-phosphate in vascular inflammatory disease

2008 ◽  
Vol 389 (11) ◽  
Author(s):  
Markus van der Giet ◽  
Markus Tölle ◽  
Burkhard Kleuser
Keyword(s):  
Inflammatory Disease ◽  
Therapeutic Option ◽  
Vascular Inflammation ◽  
Vascular Diseases ◽  
Receptor Activation ◽  
Pathological Feature ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Anti Inflammatory

Abstract The typical pathological feature of atherosclerosis is inflammation. In the last years, it has become evident that inhibition of inflammation is one important therapeutic option in atherosclerosis. Recently, sphingolipid sphingosine-1-phosphate (S1P) was identified as a crucial molecule with potent anti-inflammatory properties. Indeed, S1P activates various G protein-coupled receptors, namely S1P1–S1P5. In the vasculature, mainly S1P1–3 receptors are present. FTY720, after phosphorylation to FTY720-P, is an orally active S1P mimetic. FTY720 has been developed for therapy in the field of autoimmune diseases and organ transplantation. In analogy to S1P, FTY720 shows potent anti-inflammatory effects and several groups have tested the in vivo effects of FTY720 on the progression of inflammatory vascular diseases. They could show that S1P receptor activation might lead to a partial inhibition of the progression of atherosclerotic lesions. S1P receptor activation therefore might be a concept for anti-inflammatory drug treatment. However, it is not clear how S1P and FTY720 exactly act on vascular inflammation. This review article gives a brief overview over the known actions of S1P in vascular inflammatory disease.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Controlling Hypertension and Stroke Prevention – From Guideline to Clinical Practice

2011 ◽  
Vol 3 (1) ◽  
pp. 30
Author(s):  
Anding Xu ◽  
Zefeng Tan ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Stroke Prevention ◽  
Modifiable Risk Factors ◽  
Cerebrovascular Events

Hypertension is the most important of the prevalent and modifiable risk factors for stroke. Based on evidence, blood pressure (BP) lowering is recommended in guidelines for the prevention of stroke. However, there are still some uncertainties in the guidelines for controlling BP and preventing stroke in patients with previous cerebrovascular events, such as the goal BP, who to treat and which class of BP-lowering drugs to use. This article discusses these questions by reviewing guidelines and corresponding clinical trials, with the aim of reducing the gap between guidelines and clinical practice.

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