Matrix Metalloproteinase-2 Is Associated with Tenascin-C in Calcific Aortic Stenosis

Jiang, Bo; Jones, Peter; Li, Quanyi; Mohler, Emile R.; Schoen, Frederick J.; Levy, Robert J.

doi:10.1016/s0002-9440(10)61698-7

Cited by 153 publications

(117 citation statements)

References 30 publications

(27 reference statements)

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Section: Calcificationmentioning

confidence: 99%

“…12 They also contain tenascin C, 66 an extracellular matrix glycoprotein found in developing bones. 66 Recently, groups have isolated a subset of valvular fibroblasts that express osteoblast markers 57,65 and spontaneously form hydroxyapatite-containing calcified nodules in vitro. 57,65 In response to oxidized cholesterol, 57 transforming growth factor (TGF) ␤1, 57 BMP2, 57 and RANKL, 65 these cells increase their expression of osteoblast markers and increase their rate of calcified nodule formation.…”

Section: Calcificationmentioning

confidence: 99%

“…In addition, tenascin C upregulates matrix metalloproteinase (MMP)-2 expression in these cells. 66 Importantly, it recently has been shown that statins inhibit calcified nodule formation in these cells, at least in part through inhibition of protein prenylation. 58 Finally, hyperphosphatemia has been shown to induce calcified vesicle formation in myofibroblasts, 67 thereby suggesting a potential mechanism linking chronic kidney disease to valvular calcification.…”

Section: Calcificationmentioning

confidence: 99%

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Pathogenesis of Calcific Aortic Valve Disease

O’Brien

2006

ATVB

252

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Background-Over the past 10 to 15 years, calcific aortic valve disease, which includes aortic sclerosis and aortic stenosis, has come to be recognized as an active process, based on: (1) epidemiologic studies demonstrating associations of specific risk factors with increased prevalence or rate of progression of aortic valve disease; (2) identification, in valve lesions, of histopathologic features of chronic inflammation, lipoprotein deposition, renin-angiotensin system components, and molecular mediators of calcification; and (3) identification of cell-signaling pathways and genetic factors that may participate in valve disease pathogenesis. These studies will be reviewed and organized into a proposed global hypothesis for the pathogenesis of calcific aortic valve disease. Key Words: aortic valve disease Ⅲ calcification Ⅲ lipoproteins Ⅲ matrix Ⅲ angiotensin II C alcific aortic valve disease is identified by thickening and calcification of the aortic valve leaflets in the absence of rheumatic heart disease. It is divided, on a functional basis, into aortic sclerosis, in which the leaflets do not obstruct left ventricular outflow, and aortic stenosis, in which obstruction to left ventricular outflow is present. Aortic sclerosis is present in more than 25% of patients over age 65 1 and is associated with a 50% increase risk of cardiovascular events. 2 Aortic stenosis is present in 2% to 5% of very elderly patients, 1,3 is the second most common indication for cardiac surgery, 4 and carries an 80% 5-year risk of progression to heart failure, valve replacement, or death. 5 Though the disease is associated with substantial clinical consequences, there currently is no effective therapy for the disease other than surgical aortic valve replacement.The lack of medical therapies for calcific aortic valve disease can be traced to at least two important issues, one intellectual, the other practical. The first was the long-held notion that calcific aortic valve disease was a "degenerative," and therefore unmodifiable, condition. 6 However, more recent studies have demonstrated convincingly that calcific aortic valve lesions have many features characteristic of an active pathobiological process, including chronic inflammation, 7-9 lipoprotein deposition, 10 -12 active calcification, [13][14][15][16][17][18] and renin-angiotensin system activation. 19,20 These features are present in both trileaflet and bileaflet aortic valve lesions. 21 Also, an emerging body of literature is investigating how genetic factors might influence disease development. [22][23][24][25] The second issue is that, for many years, there were no animal models that faithfully replicated the key histological features of the disease. Recently, rabbit models been developed, 16,26,27 with that of Rajamannan and colleagues already providing a number of novel insights. 16 -18,28,29 In particular, these models have implicated the Wnt 18 and Runx2/ Cbfa1 16,17,27 signaling pathways in disease pathogenesis. Only very recently has a purported mouse model of calcif...

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Section: Calcificationmentioning

confidence: 99%

Section: Calcificationmentioning

confidence: 99%

Section: Calcificationmentioning

confidence: 99%

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Pathogenesis of Calcific Aortic Valve Disease

O’Brien

2006

ATVB

252

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“…Streptococcus pyogenes throat infection triggers an inflammatory reaction that involves several proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), IL-1, and IL-6 (5). Immunohistochemical studies have shown expression of TnC in patients with congenital aortic valve stenosis (9,10). Moreover, a recent study reported that TNFα, interferon gamma (IFNγ) and TnC concentrations in patients with rheumatic HVD were significantly higher than those with congenital valvular malformation and normal controls.…”

Section: Introductionmentioning

confidence: 99%

The role of tenascin-C and oxidative stress in rheumatic and congenital heart valve diseases: an observational study

Karataş¹,

Baysal²,

Şap³

et al. 2013

Anadolu Kardiyol Derg

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Objective: The aim of this study was to evaluate the association of tenascin-C (TnC) and total oxidant-antioxidant status to rheumatic or congenital heart valve diseases (HVD) in pediatric patients. Methods: Fifty pediatric patients (25 rheumatic HVD patients and 25 congenital HVD patients) and 20 healthy age-matched control subjects, aged 3-17 years, were enrolled in this observational and cross-sectional study. Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI) and TnC levels were compared among the groups. ANOVA and Kruskal-Wallis tests were used for statistical analysis. Results: Serum TnC level of the patients with rheumatic HVD [median 9.09 (0.94-46.30) ng/mL] was significantly higher than both congenital HVD and control groups [median 2.97 (0.66-11.80) ng/mL; p<0.01, 4.72±1.77 ng/mL; p<0.05, respectively]. However, there was no statistically significant difference between the congenital and control groups in terms of serum TnC level. The levels of serum TAC, TOS and OSI were found to be statistically similar in all groups. In addition, there were no correlations between the level of TnC, and TOS and OSI. Conclusion: Tenascin-C can be used as a biochemical marker in the differential diagnosis of rheumatic and congenital HVD. As the oxidant and antioxidant systems were found to be in equilibrium in rheumatic and congenital HVD, oxidative stress can be thought not to have a marked role in the etiopathogenesis of rheumatic HVD during childhood. (Anadolu Kardiyol Derg 2013; 13: 350-6) Key words: Children, rheumatic valve disease, congenital valve disease, tenascin-C, total antioxidant capacity, total oxidant status Original Investigation Özgün Araşt›rma 350ÖZET Amaç: Bu çalışmanın amacı çocukluk döneminde romatizmal veya konjenital kapak hastalıklarının serum tenascin-C (TnC) ve total oksidan-antioksidan seviyeleri ile ilişkisini değerlendirmektir. Yöntemler: Yaşları 3-17 arasındaki 50 çocuk hasta (25 romatizmal kapak hastası, 25 konjenital kapak hastası) ile yaşça uyumlu 20 sağlıklı birey bu enine kesitli ve gözlemsel çalışmaya alındı. Tenascin-C, total anti-oksidan kapasite (TAC), total oksidan seviye (TOS) ve oksidatif stres indeks (OSİ) değerleri gruplar arasında karşılaştırıldı. Gruplar arası karşılaştırmalarda ANOVA ve Kruskal-Wallis testi kullanıldı. Bulgular: Romatizmal kalp hastalığı grubunun TnC düzeyleri [ortanca 9.09 (0.94-46.30) ng/mL] konjenital ve kontrol gruplarından yüksek bulundu [sırasıyla ortanca 2.97 (0.66-11.80) ng/mL, p<0.01; 4.72±1.77 ng/mL, p<0.05]. Ancak konjenital grup ile kontrol grubunun TnC düzeyleri arasında istatistiksel olarak anlamlı bir farklılık saptanmadı. Gruplar arasında TAC, TOS ve OSI değerleri açısından da farklılık saptanmadı. Tenascin-C düzeyi ile TOS ve OSI arasında da korelasyon saptanmadı. Sonuç: Tenascin-C, romatizmal kapak hastalıkları ile konjenital kapak hastalıkları ayırıcı tanısında bir biyokimyasal marker olarak kullanılabilir. Romatizmal ve konjenital kapak hastalıklarında oksidan ve antioksidan sisteml...

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“…Молекулярно-генетические механизмы процессов фиброза и ремоделирования МКМ при АС Механизмы ремоделирования МКМ при АС были изучены на примере ММР и катепсинов, ферментов, участвующих в деградации межклеточного матрикса: ММР 1,2,3,7,9,12 и их ингибиторов (TIMP1,2,3,4), катепсинов S, K, V, G, трансформирующего фактора роста β1(TGFβ1) [16,[48][49][50], TNF-α [51], тенасцина С [52]. Генетические полиморфизмы ММР и катеп-синов не изучались, однако высокий уровень экс-прессии гена ММР (в частности, ММР 1,7,9,12) и ТИМР 1,2 в образцах самих клапанов при морфоло-гическом исследовании был ассоциирован с АС [21].…”

Section: кальциевый обменunclassified