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Advances in Clinical and Experimental... Dec 2018Atherosclerosis (AS) is one of the most prevalent causes of death around the world. Since there are different types of risk factors, different types of medications focus...
BACKGROUND
Atherosclerosis (AS) is one of the most prevalent causes of death around the world. Since there are different types of risk factors, different types of medications focus on preventing atheromas and plaques from establishing or on preventing established plaques from growing.
OBJECTIVES
The aim of this study was to evaluate the effect of all-trans retinoic acid (atRA) on AS in a rabbit model of fat-induced AS.
MATERIAL AND METHODS
Atherosclerosis was induced by a high-fat diet (HFD) for 75 days. Thirty rabbits were randomly divided into 5 groups. Group 1 was the negative control group and received a normal diet. The animals in the other groups were fed a HFD. Group 2 (the AS positive control group) received no drugs, Group 3 received atorvastatin orally (20 mg/kg/day), Group 4 received atRA (5 mg/kg/day, orally), and Group 5 received both drugs. All medications were started on day 45 and continued until the end of the study. Fasting blood samples were obtained for lipid profile evaluation. The aorta sections were evaluated for maximum wall and intima thickness.
RESULTS
Oral administration of atRA, atorvastatin or their combination significantly improved serum lipid profile (p < 0.001). Atorvastatin and atRA significantly decreased serum total cholesterol and LDL-cholesterol levels in HFD (p < 0.001). No difference was found in serum HDL-cholesterol levels among the studied groups. The HFD group (Group 2 - positive control) showed significant intima irregularities with fat deposition and foamy macrophage accumulation (atheroma). Administration of atRA and atorvastatin significantly decreased the size of atherosclerotic plaques (intima thickness). The maximum vessel wall and intima thickness were significantly decreased after atRA and atorvastatin administration (p < 0.001). No difference was found between atRA and atorvastatin effectiveness, but combination therapy significantly decreased AS size in comparison to using either of the drugs alone (p < 0.001).
CONCLUSIONS
In reducing AS plaque size, atRA is as effective as atorvastatin. Additionally, the combination therapy of atRA and atorvastatin decreased AS size much more effectively, showing their synergistic effect. atRA can also improve the serum lipid profile.
Topics: Animals; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Diet, High-Fat; Hypercholesterolemia; Lipids; Plaque, Atherosclerotic; Rabbits; Random Allocation; Tretinoin; Tunica Intima
PubMed: 30048051
DOI: 10.17219/acem/74552 -
Scientific Reports Jul 2020Cerebral aneurysms are abnormal focal dilatations of arterial vessel walls with pathological vessel structure alterations. Sudden rupture can lead to a subarachnoid...
Cerebral aneurysms are abnormal focal dilatations of arterial vessel walls with pathological vessel structure alterations. Sudden rupture can lead to a subarachnoid hemorrhage, which is associated with a high mortality. Therefore, the origin of cerebral aneurysms as well as the progression to the point of rupture needs to be further investigated. Label-free multimodal multiphoton microscopy (MPM) was performed on resected human aneurysm domes and integrated three modalities: coherent anti-Stokes Raman scattering, endogenous two-photon fluorescence and second harmonic generation. We showed that MPM is a completely label-free and real-time powerful tool to detect pathognomonic histopathological changes in aneurysms, e.g. thickening and thinning of vessel walls, intimal hyperplasia, intra-wall haemorrhage, calcification as well as atherosclerotic changes. In particular, the loss or fragmentation of elastin as well as fibromatous wall remodelling appeared very distinct. Remarkably, cholesterol and lipid deposits were clearly visible in the multiphoton images. MPM provides morphological and biochemical information that are crucial for understanding the mechanisms of aneurysm formation and progression.
Topics: Humans; Intracranial Aneurysm; Intracranial Arteriosclerosis; Microscopy, Fluorescence, Multiphoton; Spectrum Analysis, Raman; Tunica Intima; Vascular Calcification
PubMed: 32704100
DOI: 10.1038/s41598-020-69222-5 -
BMC Cardiovascular Disorders Sep 2008Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and... (Meta-Analysis)
Meta-Analysis Randomized Controlled Trial Review
The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis.
BACKGROUND
Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.
METHODS
We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.
RESULTS
After a mean treatment period of 3.9 +/- 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 micromol/L, 95% CI 7.5 to 8.4 versus 11.8 micromol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 +/- 0.17 mm vitamins versus 0.83 +/- 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.
CONCLUSION
Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.
Topics: Aged; Carotid Arteries; Dietary Supplements; Double-Blind Method; Down-Regulation; Drug Combinations; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Regional Blood Flow; Stroke; Time Factors; Treatment Outcome; Tunica Intima; Tunica Media; Vasodilation; Vitamin B 12; Vitamin B 6; Vitamin B Complex
PubMed: 18803866
DOI: 10.1186/1471-2261-8-24 -
Journal of Atherosclerosis and... Feb 2006This review summarizes both the structure and function of IL-1 receptor antagonist (IL-1Ra), and relates our new findings, particularly those obtained in... (Review)
Review
This review summarizes both the structure and function of IL-1 receptor antagonist (IL-1Ra), and relates our new findings, particularly those obtained in IL-1Ra-deficient mice (IL-1Ra(-/-)), to the role of IL-1Ra in arterial diseases and cholesterol metabolism. IL-1Ra(-/-) mice show an increase in neointima-formation after arterial injury. Heterozygosity in the IL-1Ra gene against the apolipoprotein E-deficient background revealed a role for IL-1 in promoting atherogenic cell signaling and that the larger lesions of IL-1Ra(-/-) mice are enriched in macrophages and depleted of smooth muscle cells. Furthermore, IL-1Ra(-/-) mice developed severe fatty livers and hypercholesteroremia following 20 weeks on a atherogenic diet compared to WT mice. Taken together, these results suggest that IL-1Ra plays important roles in restenosis after angioplasty, the development of atherosclerosis, and the metabolism of cholesterol in vivo.
Topics: Animals; Atherosclerosis; Cholesterol; Humans; Interleukin 1 Receptor Antagonist Protein; Recombinant Proteins; Sialoglycoproteins; Tunica Intima
PubMed: 16505588
DOI: 10.5551/jat.13.21 -
Annals of the Rheumatic Diseases Sep 2006Chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis are associated with accelerated atherosclerosis. We hypothesised that...
OBJECTIVE
Chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis are associated with accelerated atherosclerosis. We hypothesised that atherosclerosis may also be increased in Takayasu arteritis.
METHODS
The frequency of atherosclerotic plaques and the intima-media thickness (IMT) were investigated in 30 female patients with Takayasu arteritis (mean age (standard deviation), 35.4 (8.0) years), along with 45 sex-matched and age-matched patients with SLE (37.4 (6.8)) and 50 healthy controls (38.2 (5.7)). Plaques were scanned and IMT was measured at both sides of the common carotids, carotid bulb, and internal and external carotid arteries by B-mode ultrasonography. Traditional risk factors for atherosclerosis were also assessed.
RESULTS
Most of the atherosclerotic risk factors were comparable between patients with Takayasu arteritis and SLE. More atherosclerotic plaques were observed among patients with Takayasu arteritis (8/30; 27%) and those with SLE (8/45; 18%) than among the healthy controls (1/50; 2%; p = 0.005). Logistic regression analyses showed that the presence of a plaque was associated only with age in both Takayasu arteritis and SLE (p = 0.04 and 0.02, respectively). The mean overall IMT was significantly higher among patients with Takayasu arteritis (0.95+/-0.31 mm) than among the patients with SLE (0.58+/-0.10 mm) and the healthy controls (0.59+/-0.08 mm; p<0.001).
CONCLUSION
Patients with Takayasu arteritis have a high rate of atherosclerotic plaques, at least as frequent as that observed among patients with SLE.
Topics: Adolescent; Adult; Age Factors; Atherosclerosis; Carotid Arteries; Case-Control Studies; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Risk Factors; Takayasu Arteritis; Tunica Intima; Tunica Media; Ultrasonography
PubMed: 16439439
DOI: 10.1136/ard.2005.047498 -
Frontiers in Immunology 2018Plaque microvascularization and increased endothelial permeability are key players in the development of atherosclerosis, from the initial stages of plaque formation to... (Review)
Review
Plaque microvascularization and increased endothelial permeability are key players in the development of atherosclerosis, from the initial stages of plaque formation to the occurrence of acute cardiovascular events. First, endothelial dysfunction and increased permeability facilitate the entry of diverse inflammation-triggering molecules and particles such as low-density lipoproteins into the artery wall from the arterial lumen and vasa vasorum (VV). Recognition of entering particles by resident phagocytes in the vessel wall triggers a maladaptive inflammatory response that initiates the process of local plaque formation. The recruitment and accumulation of inflammatory cells and the subsequent release of several cytokines, especially from resident macrophages, stimulate the expansion of existing VV and the formation of new highly permeable microvessels. This, in turn, exacerbates the deposition of pro-inflammatory particles and results in the recruitment of even more inflammatory cells. The progressive accumulation of leukocytes in the intima, which trigger proliferation of smooth muscle cells in the media, results in vessel wall thickening and hypoxia, which further stimulates neoangiogenesis of VV. Ultimately, this highly inflammatory environment damages the fragile plaque microvasculature leading to intraplaque hemorrhage, plaque instability, and eventually, acute cardiovascular events. This review will focus on the pivotal roles of endothelial permeability, neoangiogenesis, and plaque microvascularization by VV during plaque initiation, progression, and rupture. Special emphasis will be given to the underlying molecular mechanisms and potential therapeutic strategies to selectively target these processes.
Topics: Adaptation, Biological; Animals; Atherosclerosis; Biomarkers; Capillary Permeability; Cardiovascular Diseases; Disease Models, Animal; Disease Progression; Disease Susceptibility; Endothelial Cells; Energy Metabolism; Epigenesis, Genetic; Humans; MicroRNAs; Neovascularization, Pathologic; Plaque, Atherosclerotic; Risk Factors; Tunica Intima; Vasa Vasorum; Vasculitis
PubMed: 29719532
DOI: 10.3389/fimmu.2018.00706 -
Scientific Reports Jul 2018It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated...
It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression.
Topics: Aged; Aged, 80 and over; Animals; Arteries; Body Mass Index; Down-Regulation; Endothelium, Vascular; Female; Glucagon-Like Peptide-1 Receptor; Human Umbilical Vein Endothelial Cells; Humans; Male; Middle Aged; Obesity; RNA, Small Interfering; Transcription Factor 7-Like 2 Protein; Tunica Intima; Tunica Media
PubMed: 30006590
DOI: 10.1038/s41598-018-28849-1 -
Turk Kardiyoloji Dernegi Arsivi : Turk... Dec 2012
Topics: Coronary Artery Disease; Humans; Tunica Intima; Vascular Calcification
PubMed: 23518880
DOI: 10.5543/tkda.2012.60308 -
Journal of Atherosclerosis and... 2004Evaluation of carotid intima media wall thickness (IMT) by using ultrasonography is a validated quantitative method for assessing atherosclerosis, and is closely... (Comparative Study)
Comparative Study Review
Evaluation of carotid intima media wall thickness (IMT) by using ultrasonography is a validated quantitative method for assessing atherosclerosis, and is closely correlated with pathological findings observed in the carotid artery. Furthermore, the appearance of atherosclerosis in the carotid artery has been highly associated with atherosclerosis in the aorta and a close relationship has been observed between IMT and the incidence of coronary heart disease. In the present study, we investigated the association of risk factors for atherosclerosis with pre-clinical atherosclerosis as evaluated by IMT in native Japanese and Japanese Americans living in the United States.
Topics: Aged; Arteriosclerosis; Asian; Diabetes Complications; Female; Humans; Japan; Life Style; Male; Middle Aged; Obesity; Risk Factors; Tunica Intima; Ultrasonography; United States
PubMed: 15644586
DOI: 10.5551/jat.11.330 -
American Journal of Physiology. Heart... Sep 2018The microstructure of arteries, consisting, in particular, of collagen, elastin, and vascular smooth muscle cells, plays a very significant role in their biomechanical... (Review)
Review
The microstructure of arteries, consisting, in particular, of collagen, elastin, and vascular smooth muscle cells, plays a very significant role in their biomechanical response during a cardiac cycle. In this article, we highlight the microstructure and the contributions of each of its components to the overall mechanical behavior. We also describe the changes of the microstructure that occur as a result of abdominal aortic aneurysms and disease, such as atherosclerosis. We also focus on how the passive and active constituents are incorporated into a mathematical model without going into detail of the mathematical formulation. We conclude by mentioning open problems toward a better characterization of the biomechanical aspects of arteries that will be beneficial for a better understanding of cardiovascular pathophysiology.
Topics: Animals; Arteries; Biomechanical Phenomena; Hemodynamics; Humans; Models, Cardiovascular; Tunica Intima; Tunica Media
PubMed: 29799274
DOI: 10.1152/ajpheart.00117.2018