scholarly journals Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 459
Author(s):  
Raphaëlle Bourgeois ◽  
Jérôme Bourgault ◽  
Audrey-Anne Despres ◽  
Nicolas Perrot ◽  
Jakie Guertin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Aortic Valve ◽  
Biological Pathways ◽  
Label Free ◽  
Aortic Valves ◽  
Lipoprotein A ◽  
Protein Activation ◽  
Molecular Events ◽  
Transcriptomic Signature ◽  
Activation Cascade

Lipoprotein(a) (Lp(a)) is one of the most important risk factors for the development of calcific aortic valve stenosis (CAVS). However, the mechanisms through which Lp(a) causes CAVS are currently unknown. Our objectives were to characterize the Lp(a) proteome and to identify proteins that may be differentially associated with Lp(a) in patients with versus without CAVS. Our second objective was to identify genes that may be differentially regulated by exposure to high versus low Lp(a) levels in explanted aortic valves from patients with CAVS. We isolated Lp(a) from the blood of 21 patients with CAVS and 22 volunteers and performed untargeted label-free analysis of the Lp(a) proteome. We also investigated the transcriptomic signature of calcified aortic valves from patients who underwent aortic valve replacement with high versus low Lp(a) levels (n = 118). Proteins involved in the protein activation cascade, platelet degranulation, leukocyte migration, and response to wounding may be associated with Lp(a) depending on CAVS status. The transcriptomic analysis identified genes involved in cardiac aging, chondrocyte development, and inflammation as potentially influenced by Lp(a). Our multi-omic analyses identified biological pathways through which Lp(a) may cause CAVS, as well as key molecular events that could be triggered by Lp(a) in CAVS development.

scholarly journals Label-Free Investigations on the G Protein Dependent Signaling Pathways of Histamine Receptors

2021 ◽  
Vol 22 (18) ◽  
pp. 9739 ◽  
Author(s):  
Ulla Seibel-Ehlert ◽  
Nicole Plank ◽  
Asuka Inoue ◽  
Guenther Bernhardt ◽  
Andrea Strasser
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Drug Targets ◽  
Physiological Role ◽  
Histamine Receptors ◽  
Label Free ◽  
Knock Out ◽  
Protein Activation ◽  
Hek Cells ◽  
Molecular Events

G protein activation represents an early key event in the complex GPCR signal transduction process and is usually studied by label-dependent methods targeting specific molecular events. However, the constrained environment of such “invasive” techniques could interfere with biological processes. Although histamine receptors (HRs) represent (evolving) drug targets, their signal transduction is not fully understood. To address this issue, we established a non-invasive dynamic mass redistribution (DMR) assay for the human H1–4Rs expressed in HEK cells, showing excellent signal-to-background ratios above 100 for histamine (HIS) and higher than 24 for inverse agonists with pEC50 values consistent with literature. Taking advantage of the integrative nature of the DMR assay, the involvement of endogenous Gαq/11, Gαs, Gα12/13 and Gβγ proteins was explored, pursuing a two-pronged approach, namely that of classical pharmacology (G protein modulators) and that of molecular biology (Gα knock-out HEK cells). We showed that signal transduction of hH1–4Rs occurred mainly, but not exclusively, via their canonical Gα proteins. For example, in addition to Gαi/o, the Gαq/11 protein was proven to contribute to the DMR response of hH3,4Rs. Moreover, the Gα12/13 was identified to be involved in the hH2R mediated signaling pathway. These results are considered as a basis for future investigations on the (patho)physiological role and the pharmacological potential of H1–4Rs.

An Assessment of Ca-Naphthenate-Epon Mixtures as Standards for Calcium Quantification in Aortic Valve Leaflets

1982 ◽  
Vol 40 ◽  
pp. 390-391
Author(s):  
Kathryn N. Colonna ◽  
Sydney S. Breese ◽  
Susan C. Sellers ◽  
J. David Deck
Keyword(s):  
Aortic Valve ◽  
Aortic Valves ◽  
X Ray ◽  
Aortic Valve Leaflets

Qualitative x-ray microanalytical studies used to demonstrate calcium in bioprosthetic aortic valves have shown that it occurs in a range of morphological forms. A consistent and reproducible standard for measuring calcium was necessary to investigate whether these forms represented varying concentrations of calcium. To provide such a standard, we tested a series of calcium naphthenate-epon mixtures.

scholarly journals Long-term survival after Carpentier-Edwards Perimount aortic valve replacement in Western Denmark: a multi-centre observational study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lytfi Krasniqi ◽  
Mads P. Kronby ◽  
Lars P. S. Riber
Keyword(s):  
Risk Factors ◽  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Significant Risk ◽  
Valve Prosthesis ◽  
Term Survival ◽  
Long Term Survival ◽  
All Cause Mortality

Abstract Background This study describes the long-term survival, risk of reoperation and clinical outcomes of patients undergoing solitary surgical aortic valve replacement (SAVR) with a Carpentier-Edwards Perimount (CE-P) bioprosthetic in Western Denmark. The renewed interest in SAVR is based on the questioning regarding the long-term survival since new aortic replacement technique such as transcatheter aortic-valve replacement (TAVR) probably have shorter durability, why assessment of long-term survival could be a key issue for patients. Methods From November 1999 to November 2013 a cohort of a total of 1604 patients with a median age of 73 years (IQR: 69–78) undergoing solitary SAVR with CE-P in Western Denmark was obtained November 2018 from the Western Danish Heart Registry (WDHR). The primary endpoint was long-term survival from all-cause mortality. Secondary endpoints were survival free from major adverse cardiovascular and cerebral events (MACCE), risk of reoperation, cause of late death, patient-prothesis mismatch, risk of AMI, stroke, pacemaker or ICD implantation and postoperative atrial fibrillation (POAF). Time-to-event analysis was performed with Kaplan-Meier curve, cumulative incidence function was performed with Nelson-Aalen cumulative hazard estimates. Cox regression was applied to detect risk factors for death and reoperation. Results In-hospital mortality was 2.7% and 30-day mortality at 3.4%. The 5-, 10- and 15-year survival from all-cause mortality was 77, 52 and 24%, respectively. Survival without MACCE was 80% after 10 years. Significant risk factors of mortality were small valves, smoking and EuroSCORE II ≥4%. The risk of reoperation was < 5% after 7.5 years and significant risk factors were valve prosthesis-patient mismatch and EuroSCORE II ≥4%. Conclusions Patients undergoing aortic valve replacement with a Carpentier-Edwards Perimount valve shows a very satisfying long-term survival. Future research should aim to investigate biological valves long-term durability for comparison of different SAVR to different TAVR in long perspective.

Platelet membrane-coated nanoparticles target sclerotic aortic valves in ApoE−/− mice by multiple binding mechanisms under pathological shear stress

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Yang ◽  
Y Song ◽  
Z Huang ◽  
J Qian ◽  
Z Pang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Binding Capacity ◽  
Platelet Membrane ◽  
Valve Disease ◽  
Funding Source ◽  
Aortic Valves ◽  
Coated Nanoparticles

Abstract Background Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesion mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE−/−) mice based on their multiple sites binding capacity under high shear stress. Methods Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo. Results Compared with PNPs bound intensity in the static station, 161%, 59%, and 39% of attached PNPs remained adherent on VWF-, collagen-, and fibrin-coated surfaces under shear stress of 25dyn/cm2 respectively. PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE−/− mice, PNPs group exhibited significant increase of accumulation in the aortic valves compared with PBS and control NP group. PNPs displayed high degrees of proximity or co-localization with vWF, collagen and fibrin, which exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms. Conclusion PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease. Targeting combination Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China

Presence of adipose tissue in aortic valves from aortic regurgitation patients: pathophysiological role and clinical implications

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Sadaba Cipriain ◽  
A.M Navarro Echeverria ◽  
C.R Tiraplegui Garjon ◽  
A Garcia De La Pena Urtasun ◽  
V Arrieta Paniagua ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Aortic Valve ◽  
Aortic Regurgitation ◽  
Systolic Function ◽  
Statistical Significance ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Funding Source ◽  
Matrix Remodeling ◽  
Aortic Valves

Abstract Introduction Adipose tissue is a common constituent of the heart and it is located, without great clinical relevance, frequently in the pericardium. The presence of adipose tissue in the aortic valve is rare, with unknown significance on valve structural properties and function. Aortic regurgitation (AR) is the third most prevalent valve disease, although it is uncommon to find it in isolation. Myxoid degeneration may be the cause or result of AR, although the pathophysiology remains poorly understood. Purpose To describe and characterize the presence of adipose tissue in the aortic valves from a cohort of AR patients. Methods 116 patients undergoing aortic valve replacement due to severe AR were enrolled. We classified them in two groups according to the histological results showing presence or absence of adipose tissue in the aortic valves. In the valve tissue molecular analysis were performed by RT-PCR, Western Blot and ELISA to analyze markers of adipocytes (leptin, adiponectin, resistin), inflammation (Rantes, interleukin-6, interleukin-1β), extracellular matrix remodeling (metalloproteinases-1, -2 and -9), proteoglycans (aggrecan, hyaluronan, lumican, syndecan-1, decorin) and fibrosis (collagens, fibronectin). Results Adipose tissue was found in 63% of the aortic valves analyzed. Baseline characteristics (age, hypertension, dyslipidemia, diabetes, smoking, left ventricular telediastolic diameter, left ventricular systolic function, ascending aorta) were similar in patients presenting valve adipose tissue as compared with patients without valve adipose tissue. Valves containing adipocytes exhibited a higher leptin content (p&lt;0.001), fibronectin (p&lt;0.01), decorin (p&lt;0,0001), hyaluronan (p=0.03), aggrecan (p=0.04) and metalloproteinase 1 (p=0.03). Interestingly, the presence of adipocytes in the valve was positively correlated with valve thickness measured by echocardiogram (Pearson chi2 statistical significance = 26.3345 p&lt;0.001). Conclusion To our knowledge, this is the first study that describes the presence of adipose cells in aortic valves from a cohort of AR patients. Aortic valves containing adipocytes were thicker and exhibited significant higher levels of proteoglycans, suggesting that adipocytes could contribute to the myxomatous degeneration process. Our results propose that the valve adipose tissue could play a role in the pathophysiology of AR. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Gobierno de Navarra

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