scholarly journals Anti-inflammatory and Immunomodulatory Therapies in Atherosclerosis

2021 ◽  
Author(s):  
Justine Deroissart ◽  
Florentina Porsch ◽  
Thomas Koller ◽  
Christoph J. Binder
Keyword(s):  
Lipid Lowering ◽  
Preclinical Research ◽  
Residual Cardiovascular Risk ◽  
Atherosclerosis Progression ◽  
Treatment And Prevention ◽  
Anti Inflammatory ◽  
The Cantos ◽  
Atherosclerosis Development ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Multiple Drugs

AbstractHypercholesterolemia is a major risk factor in atherosclerosis development and lipid-lowering drugs (i.e., statins) remain the treatment of choice. Despite effective reduction of LDL cholesterol in patients, a residual cardiovascular risk persists in some individuals, highlighting the need for further therapeutic intervention. Recently, the CANTOS trial paved the way toward the development of specific therapies targeting inflammation, a key feature in atherosclerosis progression. The pre-existence of multiple drugs modulating both innate and adaptive immune responses has significantly accelerated the number of translational studies applying these drugs to atherosclerosis. Additional preclinical research has led to the discovery of new therapeutic targets, offering promising perspectives for the treatment and prevention of atherosclerosis. Currently, both drugs with selective targeting and broad unspecific anti-inflammatory effects have been tested. In this chapter, we aim to give an overview of current advances in immunomodulatory treatment approaches for atherosclerotic cardiovascular diseases.

scholarly journals Statin-associated muscle symptoms: epidemiology, risk factors, mechanisms and treatment

Kardiologiia ◽  
2019 ◽  
Vol 59 (5S) ◽  
pp. 4-12
Author(s):  
A. I. Dyadyk ◽  
T. E. Kugler ◽  
S. R. Zborowskyy ◽  
Yu. V. Suliman
Keyword(s):  
Risk Factors ◽  
Clinical Manifestations ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Clinical Aspects ◽  
Lipid Lowering Therapy ◽  
Treatment And Prevention ◽  
Lowering Therapy ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Alternative Lipid

Statins are widely prescribed and the risk of adverse drug reactions of lipid-lowering therapy is actively discussed, including muscle symptoms. This review synthesizes the knowledge about the clinical aspects of statin-associated muscle symptoms, which is important for the practitioner. Potential mechanisms of their development, risk factors, clinical manifestations, treatment and prevention are described. Timely detection the side effects of statins makes it possible to diagnose and eliminate, which is crucial for conducting lipid-lowering therapy for patients with atherosclerotic cardiovascular diseases. Management of statin-associated muscle symptoms requires altering (reduced dosages, use of another statin or alternative lipid-lowering drugs) or discontinuing the statin treatment. 

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

Effects of Gentiana lutea root on vascular diseases

2020 ◽  
Vol 18 ◽  
Author(s):  
Gordana Joksic ◽  
Djordje Radak ◽  
Emina Sudar-Milovanovic ◽  
Milan Obradovic ◽  
Jelena Radovanovic ◽  
...  
Keyword(s):  
Recent Literature ◽  
Vascular Diseases ◽  
Lipid Lowering ◽  
Primary Data ◽  
Electronic Database ◽  
Active Components ◽  
Gentiana Lutea ◽  
Search Terms ◽  
Anti Oxidant ◽  
Anti Inflammatory

Background: Gentiana lutea (GL), commonly known as yellow gentian, bitter root, and bitterwort, belongs to family Gentianaceae. GL belongs to genus Gentiana, which is a rich natural source of iridoids, secoiridoids, xantones, flavonoids, triterpenoids, and carbohydrates. Medicinal plants from Gentiana species have anti-oxidant, anti-inflammatory, anti-mitogenic, anti-proliferative, and lipid-lowering effects, as well as a cardioprotective, hypotensive, vasodilator and anti-platelet activities. Objective: We reviewed the recent literature related to the effects of Gentiana species, and their active components on vascular diseases. Methods: Data used for this review were obtained by searching the electronic database [PUBMED/MEDLINE 1973 - February 2020]. The primary data search terms of interest were: Gentiana lutea, Gentienacea family, phytochemistry, vascular diseases, treatment of vascular diseases, anti-oxidant, anti-inflammatory, anti-atherogenic. Conclusion: Gentiana species and their constituents affect many different factors related to vascular disease development and progression. Therefore, Gentiana-based therapeutics represent potentially useful drugs for the management of vascular diseases.

scholarly journals Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aline Klassen ◽  
Andrea Tedesco Faccio ◽  
Carolina Raissa Costa Picossi ◽  
Priscilla Bento Matos Cruz Derogis ◽  
Carlos Eduardo dos Santos Ferreira ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density Lipoprotein Cholesterol ◽  
Residual Cardiovascular Risk ◽  
St Segment Elevation ◽  
Lipidomic Analysis ◽  
St Segment ◽  
Highly Effective

AbstractFor cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.

Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis

2018 ◽  
Vol 132 (17) ◽  
pp. 1889-1899 ◽  
Author(s):  
Dragana Dragoljevic ◽  
Marit Westerterp ◽  
Camilla Bertuzzo Veiga ◽  
Prabhakara Nagareddy ◽  
Andrew J. Murphy
Keyword(s):  
Inflammatory Diseases ◽  
Genetic Evidence ◽  
Loss Of Function ◽  
Atherosclerotic Vascular Disease ◽  
Stem And Progenitor Cells ◽  
Anti Inflammatory ◽  
The Cantos ◽  
Inflammatory Milieu ◽  
Proliferative Advantage

Cardiovascular (CV) diseases (CVD) are primarily caused by atherosclerotic vascular disease. Atherogenesis is mainly driven by recruitment of leucocytes to the arterial wall, where macrophages contribute to both lipid retention as well as the inflammatory milieu within the vessel wall. Consequently, diseases which present with an enhanced abundance of circulating leucocytes, particularly monocytes, have also been documented to accelerate CVD. A host of metabolic and inflammatory diseases, such as obesity, diabetes, hypercholesteraemia, and rheumatoid arthritis (RA), have been shown to alter myelopoiesis to exacerbate atherosclerosis. Genetic evidence has emerged in humans with the discovery of clonal haematopoiesis of indeterminate potential (CHIP), resulting in a disordered haematopoietic system linked to accelerated atherogenesis. CHIP, caused by somatic mutations in haematopoietic stem and progenitor cells (HSPCs), consequently provide a proliferative advantage over native HSPCs and, in the case of Tet2 loss of function mutation, gives rise to inflammatory plaque macrophages (i.e. enhanced interleukin (IL)-1β production). Together with the recent findings of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial that revealed blocking IL-1β using Canakinumab reduced CV events, these studies collectively have highlighted a pivotal role of IL-1β signalling in a population of people with atherosclerotic CVD. This review will explore how haematopoiesis is altered by risk-factors and inflammatory disorders that promote CVD. Further, we will discuss some of the recent genetic evidence of disordered haematopoiesis in relation to CVD though the association with CHIP and suggest that future studies should explore what initiates HSPC mutations, as well as how current anti-inflammatory agents affect CHIP-driven atherosclerosis.

scholarly journals Bergamot Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by “Junk Food”: Evidence for Anti-Inflammatory Activity

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1604 ◽  
Author(s):  
Maddalena Parafati ◽  
Antonella Lascala ◽  
Daniele La Russa ◽  
Chiara Mignogna ◽  
Francesca Trimboli ◽  
...  
Keyword(s):  
Weight Loss ◽  
Dietary Intervention ◽  
Inflammatory Activity ◽  
Lipid Lowering ◽  
Therapeutic Effects ◽  
Junk Food ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Parameters ◽  
Hepatic Fat ◽  
Anti Inflammatory

Wrong alimentary behaviors and so-called “junk food” are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The “junk food” toxicity can be studied in “cafeteria” (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

scholarly journals Capabilities of Cardioprotective Therapy in the Treatment and Prevention of Heart Failure in the Postinfarction Period

2020 ◽  
pp. 7-26
Author(s):  
Valerii Batushkin
Keyword(s):  
Heart Failure ◽  
Antihypertensive Drugs ◽  
Diastolic Pressure ◽  
Beta Blockers ◽  
Stress Test ◽  
Group Versus ◽  
Stage I ◽  
Lipid Lowering ◽  
Treatment And Prevention ◽  
Hawthorn Extract

Recently, numerous and quite convincing data has been accumulated on the effectiveness and safety of lipid-lowering drugs, beta-blockers, antiplatelet and antihypertensive drugs in patients with chronic heart failure (CHF), depending on the origin of the latter. The practitioner is suggested to use several drugs of different classes at the same time in order to reduce cardiovascular mortality, as well as the risk of recurrent myocardial infarction and ischemic stroke. In CHF, metabolism in cardiomyocytes varies depending on the stage of the disease. The changes that occur in the postinfarction period are compensatory in nature, which contributes to the partial improvement of impaired metabolism, while others, on the contrary, further inhibit the processes of energy production in the myocardium. In our research paper we will discuss some capabilities of metabolic therapy of CHF and prospects in the treatment and prevention using hawthorn extract; analyze the features of interaction of some well-known cardioprotective drugs with long-term antiplatelet therapy in the postinfarction period. Initiation of therapy with a new drug in addition to clopidogrel, such as trimetazidine, may adversely affect antiplatelet activity of clopidogrel (TRACER study, 2019). As a compromise, some herbal cardioprotective drugs may be used. Hawthorn preparations containing vaso- and cardioactive substances have significant potential in the treatment of cardiovascular diseases. Diversified mechanism of action of hawthorn has a significant impact on various parts of the cardiovascular system. Clinical trials of more than 4,000 patients confirm that standardized hawthorn extracts are effective as adjunctive therapy in the treatment of NYHA stage I–III CHF. The main two-year results of the WISO cohort study showed that the three pivotal symptoms of heart failure — fatigue (p = 0.036), stress dyspnea (p = 0.020) and palpitations (p = 0.048) — were significantly less marked after treatment in the hawthorn group versus comparative group. Cochrane analysis (2009) of studies investigating hawthorn extract included 14 studies where hawthorn was used primarily as an adjunct to conventional treatment. Exercise tolerance increased significantly during the treatment with hawthorn extract. Thus, the weighted difference between the average double multiplication rates during cardiac stress test (CST) was 122.76 W/min, whereas end-diastolic pressure in the right ventricle and myocardial oxygen consumption decreased with hawthorn treatment (a weighted mean difference was 19.22 mmHg per 1 min). The reported side effects were infrequent, mild and transient. A special hawthorn extract is indicated for the treatment of patients with NYHA stage II heart failure as an alternative and supplement to the standard evidence-based drug therapy. The beneficial effect on clinical symptoms allowed patients in the Crataegus group to reduce the use of angiotensin-converting enzyme (ACE) inhibitors from 54 to 36% (p = 0.004), cardiac glycosides from 37 to 18% (p = 0.001), diuretics from 61 to 49% (p = 0.061), beta-blockers from 33 to 22% (p = 0.052). At the same time, SPICE and HERB CHF studies show greater efficacy of Crataegus preparations in the treatment of mild to moderate heart failure (NYHA stage I–II). Higher doses (1800 mg) may be required for critically ill patients in order to achieve sustained improvement. Analysis of the data available to date is promising but suggests the need for a more focused approach to dosing based on the disease severity.

Abstract P067: HDL Particles, Immune Activation, Inflammatory and Coagulation Markers in Relation to CVD and All-Cause Mortality Among Adults Aged 80+

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Rachel H Mackey ◽  
Timothy M Hughes ◽  
Russell P Tracy ◽  
Anne B Newman ◽  
Yuefang Chang ◽  
...  
Keyword(s):  
Total Mortality ◽  
Lipid Lowering ◽  
Soluble Receptors ◽  
Cox Models ◽  
Lower Baseline ◽  
Anti Inflammatory ◽  
Response Biomarkers ◽  
D Dimer ◽  
Cvd Mortality

HDL particles, particularly small HDL particles, may be more functional (e.g. anti-inflammatory) than large HDL particles which carry more cholesterol, but levels are little affected by recent HDL-raising therapies that substantially raised HDL-C without decreasing CHD. Furthermore, lower levels of total and small HDL particles predict CHD and CVD, but have not been evaluated among elderly adults, for whom lipids are generally not positively related to CVD. Therefore, we hypothesized that among adults aged 80+, incident CVD and all-cause CVD mortality would be related to lower levels of total and small HDL particles in addition to higher levels of coagulation, inflammation and immune response biomarkers. Participants (n=162) without dementia at baseline (2001-2002) were followed through 2011 for incident CVD and total mortality. Concentrations of HDL particles (HDL-P) were measured by NMR spectroscopy (LipoScience, Inc), D-dimer, IL-6, sCD-14, and sIL-2r were measured using ELISA (R&D Systems), and soluble receptors sIL6r, and sTNFr1/r2 were measured by Multiplex Panel (Millipore) on stored baseline plasma. Among adults with mean age=83.5 years at baseline, both CVD and total mortality over 8 years follow-up (mean= 5.2 years) were associated with lower baseline levels of total and small HDL-P (but not HDL-C, large HDL-P or larger mean HDL particle size), and higher levels of IL-6, sTNFr1 and sTNFr2 (Table). Total mortality was also associated with higher levels of D-dimer and sIL2r. In Cox models adjusted for age, sex and lipid-lowering medication, lower small HDL-P remained inversely associated with total and CVD mortality, with HR (95%CI) for Q1 vs. Q4 = 3.35(1.30, 8.62) and 5.39 (1.15, 25.34) respectively, and higher IL-6 remained associated with CVD mortality HR(95% CI) for Q4 vs. Q1= 5.22 (1.10, 24.75). Among adults aged 80+, higher IL-6 and lower total and small HDL-P levels were associated with incident CVD and total mortality over 8 years, suggesting an important anti-inflammatory role for HDL particles in late life.

A novel rosuvastatin calcium cow ghee fraction biform complex: formulation characterization and evaluation

2021 ◽  
Vol 11 ◽  
Author(s):  
Vijendra Kumar Suryawanshi ◽  
Khomendra Kumar Sarwa ◽  
Suhas Narayan Sakarkar ◽  
Chanchal Deep Kaur
Keyword(s):  
Fatty Acids ◽  
Oral Bioavailability ◽  
Ex Vivo ◽  
Fatty Acid Content ◽  
Lipid Lowering ◽  
Thermal Fractionation ◽  
Ex Vivo Permeation ◽  
Anti Inflammatory ◽  
Rosuvastatin Calcium

Background: Rosuvastatin calcium is a statin class of drug having limited oral bioavailability of about 20%. This problem might be overcome by making the biform complex using cow ghee fraction as a bioavailability enhancer. Methods: A precise thermal fractionation technique was adopted to separate different fatty acids from cow ghee. Collected fractions were subjected to characterization over parameters reported for fatty acids. LC-MS and FTIR confirm the content variation in the collected fraction. Biform complex was prepared by fusion method with a constant ratio of drug and cow ghee fraction. The prepared complex was subjected to FTIR, DSC, and LC-MS study to confirm chemical composition characteristics. Drug content, in-vitro and ex-vivo permeation studies were also performed. The anti-inflammatory response was measured using the carrageenan paw-induced edema rat model. Lipid-lowering effect and inflammation marker analysis was also performed using ELISA specific kit. Results: The biform complex prepared with a thermal fraction at 30ºC of cow ghee show the highest in-vitro and ex-vivo permeation. The anti-inflammation response of the biform complex F1 was higher than other tested formulations with considerable lipid and lipoprotein lowering properties. Conclusions: This study confirms that the thermal fractionation method abled to separate cow ghee as per their fatty acid content. The complexion of rosuvastatin calcium with cow ghee thermal fraction enhances oral bioavailability followed by the anti-inflammatory and lipid-lowering activity.

Lipid-lowering Drugs

1992 ◽  
Vol 3 (2) ◽  
pp. 494-506
Author(s):  
Melinda M. Milander ◽  
Merrily Kuhn
Keyword(s):  
National Cholesterol Education Program ◽  
Diet Therapy ◽  
Lipid Lowering ◽  
Lipid Uptake ◽  
Pharmaceutical Treatment ◽  
General Reference ◽  
Treatment And Prevention ◽  
Patient Teaching ◽  
Artery Disease ◽  
Lipid Lowering Agents

Controlling hyperlipidemia is an important aspect in the treatment and prevention of coronary artery disease. This article provides the clinician with a general reference for currently used lipid-lowering agents. Lipoproteins present in the plasma are defined and a brief overview of their functions is presented. Normal lipid uptake from the intestine and normal lipid metabolism are discussed to provide a basis for an understanding of the pharmaceutical treatment of hyperlipidemia. Guidelines are reviewed for interpreting lipid profiles according to the National Cholesterol Education Program. An evaluation of the agents currently used to treat hyperlipidemia is included. Lipid-lowering agents cause alterations in liver function; therefore, patients taking these medications are monitored closely. Patient teaching, including adverse effects of the medications, diet therapy and other alterable risk factors, is also reviewed

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