DETERMINATION OF CYTOKINES AND ADHESION MOLECULES IN ELDERLY AND SENILE PATIENTS WITH AORTIC VALVE CALCIFICATION

Author(s):  
Н. А. Михеева ◽  
Н. И. Гуляев ◽  
И. Б. Олексюк ◽  
К. Л. Козлов ◽  
М. А. Соловьев ◽  
...  

Выполнено лабораторное исследование цитокинового профиля и содержания молекул межклеточной адгезии у 38 пациентов с начальными признаками кальциноза аортальных полулуний. Определено, что содержание IL -6 и IL -8 имело достоверно более высокие значения по сравнению с контрольной группой, что свидетельствует о непосредственной роли неспецифического хронического воспаления при развитии кальцинирующего поражения клапана аорты. Также было выявлено значимо более низкое содержание sE -селектина, что может говорить об отсутствии активации молекул адгезии на начальном этапе формирования кальциноза клапана аорты. Необходимо дальнейшее изучение динамики содержания sE -и sP -селектинов в процессе развития ускорения кровотока на аортальном клапане и формировании стеноза. A laboratory study of the cytokine profile and the content of the intercellular adhesion molecules was performed in 38 patients with initial signs of aortic hemilunus calcification. It has been determined that the content of IL -6 and IL -8 had significantly higher values compared with the control group, which indicates the direct role of nonspecific chronic inflammation in the development of calcifying aortic valve damage. A significantly lower content of sE -selectin was also identified, which may indicate the absence of activation of adhesion molecules at the initial stage of aortic valve calcification. Further study of the dynamics of sE - and sP -selectins content in the process of development of acceleration of blood flow in the aortic valve and the formation of stenosis is needed.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Anousakis-Vlachochristou ◽  
K Toutouzas ◽  
M Kyriakidou ◽  
E Varela ◽  
A Kapelouzou ◽  
...  

Abstract Background Advanced glycation end products (AGPs) promote human aortic smooth muscle cell calcification in vitro. Moreover, reduction of AGPs levels and inhibition of RAGE signaling decrease vascular calcification in vivo in animal studies. The role of AGPs in aortic valve calcification has not been investigated. Purpose We sought to investigate the role of AGPs in aortic valve calcification, in the absence of diabetes mellitus (DM). Methods We used human and animal cohorts. Firstly, we obtained aortic valves from patients without DM that underwent aortic valve replacement due to aortic valve stenosis. We studied the valves with Fourier-Transformed Infrared spectroscopy (FT-IR, Nicolet 6700 spectrometer, with Attenuated Total Reflection-ATR accessory, each spectrum consisted of 120 co-added spectra) in order to evaluate chemical changes. In the animal cohort, New Zealand male rabbits where randomized in calcification diet (normal chow+cholesterol 0,5%+3500 IU ergocalciferol/kg daily) and control group and sacrificed at 2, 4, 6, 8 10 and 12 weeks. The valves were longitudinally assessed with FT-IR. Results A total of 200 human aortic valves were studied (age 64–78). All patients demonstrated characteristic vibrations at the area about 1165 cm-1, where the C-O-C bonds absorb, attributed to AGPs. Thirty six rabbit valves were used, 3 per group. Glucose levels were within normal range and did not differ between groups. The FT-IR spectra of the rabbit aortic valves showed increasing intensity of the C-O-C band at 1165 cm-1 in experimental group in comparison to control group. The band at 1744 cm-1 is attributed to aldehyde formation due to oxidative stress and inflammation. Shifts and shape changes were detected at the bands of amide I and II at 1650 cm-1 and 1550 cm-1, respectively, concerning protein misfolding, fiber formation and sclerosis. The bands in the region 1299–900 cm-1 correspond to phosphate groups of phospholipidsand the formed calcium phosphate salts and non-biological hydroxyapatite Ca3(PO4)2 formation. All vibrations increased significantly longitudinally during experimental diet period. Representative FT-IR spectra of valves Conclusions Advanced glycation end products are detected in human calcified aortic valves irrespectively of DM. Moreover, AGPs correlate with presence and gradual development of aortic valve calcification in experimental rabbit model, along with acidosis, oxidation and protein secondary misfolding. Accumulation of AGPs in valve tissue is implicated in mechanisms of disease development.


2021 ◽  
Vol 5 (sup1) ◽  
pp. 73-73
Author(s):  
Megan E. Schroeder ◽  
Andrea Gonzalez Rodriguez ◽  
Kelly F. Speckl ◽  
Cierra J. Walker ◽  
Firaol S. Midekssa ◽  
...  

2020 ◽  
Vol 141 ◽  
pp. 93-104
Author(s):  
Gaigai Huang ◽  
Liqin An ◽  
Mengtian Fan ◽  
Menghao Zhang ◽  
Bin Chen ◽  
...  

2011 ◽  
Vol 29 ◽  
pp. e363
Author(s):  
A. Faustino ◽  
R. Providência ◽  
L. Paiva ◽  
P. Mota ◽  
M. Costa ◽  
...  

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Karien J Rodriguez ◽  
Laura M Piechura ◽  
Ana M Porras ◽  
Kristyn S Masters

2017 ◽  
Vol 37 (3) ◽  
pp. 543-552 ◽  
Author(s):  
Isabella Albanese ◽  
Bin Yu ◽  
Hamood Al-Kindi ◽  
Bianca Barratt ◽  
Leah Ott ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mony Shuvy ◽  
Suzan Abedat ◽  
Sameh Daher ◽  
Michael Valitsky ◽  
Ronen Beeri ◽  
...  

Aortic valve calcification (AVC) is an inflammatory regulated process. Growth arrest-specific 6 (Gas6) is involved in atherosclerosis and inflammation; in addition the Gla domain of Gas6 directly inhibits mineralization. We sought to assess the role of Gas6 in AVC using our unique animal model of reversible AVC based on a uremia-inducing diet. We also evaluated the possible role of raloxifene (a selective estrogen modulator), which has demonstrated anti inflammatory effects on blood vessels, in the pathogenesis of AVC. Aortic valves were obtained from four groups of rats (n=10 each): calcified valves- from rats fed with the uremia-inducing diet for 7 weeks (group A), valves after calcification resolution following diet cessation (group B), valves from rats fed with the same diet who also received subcutaneous raloxifen (1 mg/kg/day) (group C), and control valves. Valves were examined using multislice computed tomography (MSCT), histology, RT-PCR and western blot. Histological evaluation of calcified valves (group A) revealed positive staining for calcium deposits and osteoblast’s markers (osteopontin, Runx-2). Gene expression analyses of these valves revealed 2.5 times decrease in Gas6 level compared to control valves (p<0.01). Western blot confirmed these results, and further showed a significant decrease of 33 % in Axl (Gas6 receptor) level along with down-regulation of the AKT survival pathway. Resolution of AVC (group B) was demonstrated using MSCT and histology; it was associated with down-regulation of osteoblast features, and up-regulation of both Gas6-Axl and AKT pathways. MSCT of raloxifene treated rats (group C) showed only minimal valve calcification compared with group A (Agatston score 23 ± 7 vs. 105± 15; p< 0.05). The beneficial effect of raloxifene was also confirmed by histology and was associated with up-regulation of Gas6 and Axl (30% and 40% increase respectively compared with group A; p<0.05) and of the AKT pathway. Down-regulation of the Gas6-Axl pathway is a critical step in inducing AVC. The reversibility of AVC was associated with up-regulation of the Gas6-Axl and AKT pathways. These pathways were significantly restored by raloxifene, which may be a promising treatment for AVC.


2013 ◽  
Vol 8 (Suppl 1) ◽  
pp. O32 ◽  
Author(s):  
K Pissaridi ◽  
V Dritsa ◽  
J Anastassopoulou ◽  
E Koutoulakis ◽  
I Mamarelis ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Esteban Jorge-Galarza ◽  
Carlos Posadas-Romero ◽  
Margarita Torres-Tamayo ◽  
Aida X. Medina-Urrutia ◽  
Marco A. Rodas-Díaz ◽  
...  

Background. Insulin resistance is involved in the pathogenesis of cardiovascular disease, but its relationship with cardiovascular calcification has yielded conflicting results. The purpose of the present study was to investigate the role of hepatic and adipose tissue insulin resistance on the presence of coronary artery (CAC > 0) and aortic valve calcification (AVC > 0).Methods. In 1201 subjects (52% women,53.6±9.3years old) without familiar and personal history of coronary heart disease, CAC and AVC were assessed by multidetector-computed tomography. Cardiovascular risk factors were documented and lipid profile, inflammation markers, glucose, insulin, and free fatty acids were measured. Hepatic insulin resistance (HOMA-IR) and adipose tissue insulin resistance (Adipo-IR) indices were calculated.Results. There was a significant relationship between HOMA-IR and Adipo-IR indices (r=0.758,p<0.001). Participants in the highest quartiles of HOMA-IR and Adipo-IR indices had a more adverse cardiovascular profile and higher prevalence of CAC > 0 and AVC > 0. After full adjustment, subjects in the highest quartile of Adipo-IR index had higher odds of AVC > 0 (OR: 2.40; 95% CI: 1.30–4.43), as compared to those in the lowest quartile.Conclusions. Adipo-IR was independently associated with AVC > 0. This suggests that abnormal adipose tissue function favors insulin resistance that may promote the development and progression of AVC.


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