Aortic Valve Disease - Etiology and the Role of Vascular Pathology: Is the Face of the Disease Changing?

2002 ◽  
pp. 25-38
Author(s):  
V. Fuster ◽  
A. Rosenbluth
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Vascular Pathology ◽  
Disease Etiology ◽  
The Face

Abstract 27: Role of Sirtuin 6 in the Initiation and Progression of Calcific Aortic Valve Disease

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Carolyn M Roos ◽  
Bin Zhang ◽  
Grace Verzosa ◽  
Elise A Oehler ◽  
Michael A Hagler ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Left Ventricular Ejection ◽  
Calcific Aortic Valve Disease ◽  
Valve Calcification ◽  
Age Related ◽  
Valve Function ◽  
Osteogenic Signaling

Increasing age is a major risk factor for calcific aortic valve disease (CAVD). Interestingly, SIRT6 knockout mice have a marked progeroid phenotype, and we recently reported that sirtuin enzyme expression is dramatically reduced with aging and that SIRT6 expression is reduced further in valves from patients with end-stage CAVD. It is unknown, however, whether experimentally reducing SIRT6 promotes osteogenic signaling in the valve and ultimately accelerates progression of CAVD. Thus, we used cultured mouse aortic valve interstitial cells and ldlr-deficient, apolipoprotein B100-only mice (LA) that were SIRT6 wild-type (LA-SIRT6 +/+ ) or heterozygous (LA-SIRT6 +/- ) and fed a Western diet for 3 or 12 months to determine the role of SIRT6 in valve calcification. In vitro , reduction of SIRT6 increased histone acetylation and significantly increased mRNA and protein levels of the osteogenic genes Runx2 and Sp7 in response to bone morphogenetic protein 2 (100ng/ml BMP2 for 18 hours), and siRNA knockdown of SIRT6 increased mRNA levels of Sp7 even in the absence of exogenous bone morphogens. Using high-resolution ultrasound to evaluate aortic valve function in vivo, we found that 3 month old LA-SIRT6 +/- mice did not have significant impairments in valve function compared to LA-SIRT6 +/+ mice. In contrast, 12 month old LA-SIRT6 +/- had dramatically worsened aortic valve dysfunction and stenosis compared to LA-SIRT6 +/+ mice, which was also associated with reductions in left ventricular ejection fraction. Collectively, our data strongly suggest SIRT6 plays a critical role in the tonic repression of osteogenic signaling in the aortic valve, and that age-related reductions in SIRT6 are likely to increase susceptibility to valve calcification in response to risk factors for CAVD such as hypercholesterolemia. Collectively, increasing activity of SIRT6 or reducing acetylation of its targets may serve as viable therapeutic strategies to slow progression of age-related valvular calcification and stenosis.

Role of Ectonucleotidases and Purinergic Receptors in Calcific Aortic Valve Disease

2014 ◽  
pp. 117-126
Author(s):  
Patrick Mathieu ◽  
Ablajan Mahmut ◽  
Philippe Pibarot ◽  
Yohan Bossé ◽  
Marie-Chloé Boulanger
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Purinergic Receptors ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease

scholarly journals Investigation of the Role of Serum Matrix Gla-Protein as a Biomarker of Calcific Aortic Valve Disease

2019 ◽  
Vol 9 (3) ◽  
pp. 152-156
Author(s):  
Amal Al Nawasreh ◽  
Hussam Shebli   ◽  
Sahar Fahoum
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Matrix Gla Protein ◽  
Valve Disease ◽  
Rapid Screening ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Calcific Aortic Valve Disease ◽  
Cardiovascular Morbidity And Mortality

Background: Calcific aortic valve disease (CAVD) is a major contributor to cardiovascular morbidity and mortality. Circulating total uncarboxylated Matrix ?-carboxyglutamate (Gla) protein (t-ucMGP) is a promising biomarker for rapid screening of subjects prone to cardiovascular calcification who may need more invasive vascular diagnostics. Preliminary data show that low t-ucMGP levels are indicative for prevalent vascular calcification. Hence, the aim of our study was to investigate the possible role of circulating t-ucMGP as a biomarker may help in identification patients with CAVD, taking into consideration that CAVD is a form of vascular calcification.Methods & Materials: We analyzed serum t-ucMGP levels by enzyme-linked immunosorbent assay (ELISA) in 50 patients with echocardiographically proven CAVD and 21 control subjects.Results: Serum t-ucMGP levels were significantly lower in patients with CAVD (29.29±12.18 nmol/l) compared to the control group (36.84±21.79 nmol/l, p = 0.003).Conclusion: Serum t-ucMGP may help as a noninvasive biomarker for identification of these patients.

scholarly journals Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors

2005 ◽  
Vol 26 (13) ◽  
pp. 1333-1341 ◽  
Author(s):  
Olivier Fondard ◽  
Delphine Detaint ◽  
Bernard Iung ◽  
Christine Choqueux ◽  
Homa Adle-Biassette ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Matrix Metalloproteinases ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Tissue Inhibitors ◽  
Extracellular Matrix Remodelling ◽  
Human Aortic Valve
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