Calcific Aortic Valve Disease

Yutzey, Katherine E.; Demer, Linda L.; Body, Simon C.; Huggins, Gordon S.; Towler, Dwight A.; Giachelli, Cecilia M.; Hofmann-Bowman, Marion A.; Mortlock, Douglas P.; Rogers, Melissa B.; Sadeghi, Mehran M.; Aikawa, Elena

doi:10.1161/atvbaha.114.302523

Cited by 284 publications

(132 citation statements)

References 69 publications

(76 reference statements)

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“…However, emerging evidence has indicated that this condition is mediated by the interplay of complex biological processes that include the following: inflammation, cell apoptosis, lipids deposition, renin-angiotensin system activation, remodeling of the extracellular matrix, and bone formation [4–11]. However, the underlying mechanisms that regulate this process remain largely unknown [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Signature in Degenerative Aortic Stenosis

Shi

Liu

Wang

et al. 2016

BioMed Research International

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Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease.

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Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Signature in Degenerative Aortic Stenosis

Shi

Liu

Wang

et al. 2016

BioMed Research International

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“…Degenerative AV stenosis has become the most common type of VHD in developed countries [10], and it often involves valvular calcification. Whether the AV is especially susceptible to calcification is not clear.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors Associated with Left-Sided Cardiac Valve Calcification: A Case Control Study

Jiang

Wang²,

Xuan³

et al. 2016

Cardiology

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Objectives: To identify risk factors associated with cardiac valve calcification that is easily detectable through routine blood tests in patients who received valve replacement therapy. Methods: Four hundred patients with valvular heart disease who underwent valve replacement surgery between December 2009 and January 2013 were enrolled in this study. Of these, 77 had valve calcification; the other 323 did not. Multivariate logistic regression analysis was used to assess for risk factors associated with valve calcification. Results: In our study population, rheumatic valve lesions were the most common reason for valve replacement. Degenerative nonstenotic valve lesion was a protective factor and degenerative stenotic valve lesion was a strong risk factor for valve calcification. Serum levels of gamma-glutamyl transferase (GGT) of between 30 and 46 IU/l and >90 IU/l and total bilirubin (TBIL) of between 15 and 20 μmol/l were positively correlated with valve calcification. Meanwhile, serum calcium (Ca²⁺) levels of between 2.3 and 2.4 mmol/l were negatively correlated with rheumatic valve calcification. Conclusions: Degenerative stenotic lesion is a risk factor and degenerative nonstenotic lesion a protective factor for cardiac valve calcification. Serum GGT and TBIL levels are positively correlated and serum Ca²⁺ levels negatively correlated with rheumatic cardiac valve calcification.

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“…However, considerable evidence has now accumulated from molecular studies supporting a cell-mediated active malady involving risk factors and histopathophysiological features (endothelial cell and macrophage activation, proteolytic activity, and osteogenesis in inflamed valves with similarities to skeletal bone formation) that characterize atherosclerosis [6, 8, 9]. It was probably Leonardo da Vinci (1452–1519) [10] who first recognized atherosclerotic macroscopic changes; when he illustrated arterial atherosclerotic lesions in an elderly man at autopsy, he attributed the thickening of the vessel wall to “excessive nourishment” from the blood [11].…”

Section: Molecular Genomic and Histopathologic Aspects Of Cavdmentioning

confidence: 99%

Calcific Aortic Valve Disease: Part 1—Molecular Pathogenetic Aspects, Hemodynamics, and Adaptive Feedbacks

Pasipoularides

2016

J. of Cardiovasc. Trans. Res.

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Aortic valvular stenosis (AVS), produced by calcific aortic valve disease (CAVD) causing reduced cusp opening, afflicts mostly older persons eventually requiring valve replacement. CAVD had been considered “degenerative,” but newer investigations implicate active mechanisms similar to atherogenesis—genetic predisposition and signaling pathways, lipoprotein deposits, chronic inflammation and calcification/osteogenesis. Consequently, CAVD may eventually be controlled/reversed by lifestyle and pharmacogenomics remedies. Its management should be comprehensive, embracing not only the valve but also the left ventricle and the arterial system with their interdependent morphomechanics/hemodynamics, which underlie the ensuing diastolic and systolic LV dysfunction. Compared to even a couple of decades ago, we now have an increased appreciation of genomic and cytomolecular pathogenetic mechanisms underlying CAVD. Future pluridisciplinary studies will characterize better and more completely its pathobiology, evolution and overall dynamics, encompassing intricate feedback processes involving specific signaling molecules and gene network cascades. They will herald more effective, personalized medicine treatments of CAVD/AVS.

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Calcific Aortic Valve Disease

Cited by 284 publications

References 69 publications

MicroRNA Expression Signature in Degenerative Aortic Stenosis

MicroRNA Expression Signature in Degenerative Aortic Stenosis

Risk Factors Associated with Left-Sided Cardiac Valve Calcification: A Case Control Study

Calcific Aortic Valve Disease: Part 1—Molecular Pathogenetic Aspects, Hemodynamics, and Adaptive Feedbacks

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