Early Rescue of Lymphatic Pumping Delays Atherosclerosis Progression in Ldlr-/- Mice

2018 ◽  
Vol 32 ◽  
pp. 18
Author(s):  
Andreea Milasan ◽  
Ali Smaani ◽  
Catherine Martel
Keyword(s):  
Atherosclerosis Progression ◽  
Lymphatic Pumping

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 523-530 ◽  
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Manolis Vavuranakis ◽  
Marina Zaromytidou ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Serum Levels ◽  
Atherosclerosis Progression ◽  
Control Subjects ◽  
Significant Difference ◽  
Artery Disease ◽  
Stable Cad

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy

2020 ◽  
Vol 18 ◽  
Author(s):  
Parimalanandhini Duraisamy ◽  
Sangeetha Ravi ◽  
Mahalakshmi Krishnan ◽  
Catherene M. Livya ◽  
Beulaja Manikandan ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Atherosclerosis Progression ◽  
Proinflammatory Mediators ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Inflammatory Site

: Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

scholarly journals Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jan Pennig ◽  
Philipp Scherrer ◽  
Mark Colin Gissler ◽  
Nathaly Anto-Michel ◽  
Natalie Hoppe ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Plasma Cholesterol ◽  
Sglt2 Inhibitor ◽  
Vascular Wall ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Diabetic Mice ◽  
Glucose Lowering ◽  
Atherosclerosis Progression ◽  
Glucose Levels

AbstractDiabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68+ macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.

scholarly journals Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe

2020 ◽  
Vol 6 (50) ◽  
pp. eabc2697
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Chung Hwee Thiam ◽  
Syaza Hazwany Azhar ◽  
Caris Tan ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Lymphatic Drainage ◽  
Lymphatic Transport ◽  
Atherosclerotic Plaques ◽  
Tissue Fluid ◽  
Atherosclerosis Progression ◽  
Lymphatic Vasculature ◽  
Lesion Regression ◽  
Transport Of Macromolecules

A functional lymphatic vasculature is essential for tissue fluid homeostasis, immunity, and lipid clearance. Although atherosclerosis has been linked to adventitial lymphangiogenesis, the functionality of aortic lymphatic vessels draining the diseased aorta has never been assessed and the role of lymphatic drainage in atherogenesis is not well understood. We develop a method to measure aortic lymphatic transport of macromolecules and show that it is impaired during atherosclerosis progression, whereas it is ameliorated during lesion regression induced by ezetimibe. Disruption of aortic lymph flow by lymphatic ligation promotes adventitial inflammation and development of atherosclerotic plaque in hypercholesterolemic mice and inhibits ezetimibe-induced atherosclerosis regression. Thus, progression of atherosclerotic plaques may result not only from increased entry of atherogenic factors into the arterial wall but also from reduced lymphatic clearance of these factors as a result of aortic lymph stasis. Our findings suggest that promoting lymphatic drainage might be effective for treating atherosclerosis.

scholarly journals Oxidative Stress Biomarkers, Nut-Related Antioxidants, and Cardiovascular Disease

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 682 ◽  
Author(s):  
Julia Lorenzon dos Santos ◽  
Alexandre Schaan de Quadros ◽  
Camila Weschenfelder ◽  
Silvia Bueno Garofallo ◽  
Aline Marcadenti
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Cardiovascular Prevention ◽  
Food Sources ◽  
Dietary Antioxidants ◽  
Oxidative Stress Biomarkers ◽  
Atherosclerosis Progression ◽  
Coronary Syndrome ◽  
Biomarkers Of Oxidative Stress

Atherosclerosis is related to fat accumulation in the arterial walls and vascular stiffening, and results in acute coronary syndrome which is commonly associated with acute myocardial infarction. Oxidative stress participates in the pathogenesis of atherosclerosis. Thus, the inclusion of food sources of dietary antioxidants, such as different kinds of nuts, may improve biomarkers related to oxidative stress, contributing to a possible reduction in atherosclerosis progression. This article has briefly highlighted the interaction between oxidative stress, atherosclerosis, and cardiovascular disease, in addition to the effect of the consumption of different nuts and related dietary antioxidants—like polyphenols and vitamin E—on biomarkers of oxidative stress in primary and secondary cardiovascular prevention. Studies in vitro suggest that nuts may exert antioxidant effects by DNA repair mechanisms, lipid peroxidation prevention, modulation of the signaling pathways, and inhibition of the MAPK pathways through the suppression of NF-κB and activation of the Nrf2 pathways. Studies conducted in animal models showed the ability of dietary nuts in improving biomarkers of oxidative stress, such as oxLDL and GPx. However, clinical trials in humans have not been conclusive, especially with regards to the secondary prevention of cardiovascular disease.

Oxidized Lipoproteins in Blood Plasma: Possible Marker of Atherosclerosis Progression

IUBMB Life ◽  
1999 ◽  
Vol 48 (4) ◽  
pp. 413-417
Author(s):  
Patricia Moriel ◽  
Fabio S. Okawabata ◽  
Dulcineia S. P. Abdalla
Keyword(s):  
Blood Plasma ◽  
Atherosclerosis Progression ◽  
Oxidized Lipoproteins ◽  
In Blood Plasma
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