Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis

Kaden, Jens J.; Dempfle, Carl-Erik; Grobholz, Rainer; Tran, Hanh-Thai; Kılıç, Refika; Sarıkoç, Aslıhan; Brueckmann, Martina; Vahl, Christian F.; Hagl, S.; Haase, Karl K.; Borggrefe, Martin

doi:10.1016/s0021-9150(03)00284-3

Cited by 221 publications

(156 citation statements)

References 29 publications

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“…[7][8][9] One also found expression of important chronic inflammation effector molecules, including interleukin (IL)-2 and the Class II human leukocyte antigen, HLA-DR. 9 More recently, mast cells 20 and the proinflammatory cytokines, IL-1␤ 45 and tumor necrosis factor (TNF)-␣, 46 also have been identified in stenotic aortic valves. In addition, aortic valve lesions contain a number of matrix-metalloproteinases (MMPs), [45][46][47][48] which degrade various components of the extracellular matrix. Results differ as to whether levels of the natural inhibitors of MMPs, tissue inhibitors of matrix metalloproteinases (TIMPs), are increased 48 or unchanged 46 in valve lesions.…”

Section: Chronic Inflammationmentioning

confidence: 99%

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: Chronic Inflammationmentioning

confidence: 99%

Pathogenesis of Calcific Aortic Valve Disease

O’Brien

2006

ATVB

252

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“…CAS is characterized by valve thickening and stenosis of the orifice area triggered by an overactive inflammatory process involving expression of cytokines, including tumor necrosis factor-a (TNF-a) [2], transforming growth factor-beta 1 [3], and interleukin-1 beta (IL-1beta) [4]. These cytokines contribute to extracellular matrix formation, remodeling, and ectopic calcification, which are accelerated in the presence of high inorganic phosphate (2.2-3.2 mM) [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

CD34-negative mesenchymal stem-like cells may act as the cellular origin of human aortic valve calcification

Nomura

Seya

et al. 2013

Biochemical and Biophysical Research Communications

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Although various osteogenic inducers contribute to the calcification of human aortic valve interstitial cells, the cellular origin of calcification remains unclear. We immunohistochemically investigated the cellular origin of valve calcification using enzymatically isolated cells from both calcified and non-calcified human aortic valve specimens. CD73-, 90-, and 105-positive and CD45-negative mesenchymal stem-like cells (MSLCs) were isolated from both types of valve specimens using fluorescence-activated cell sorting. MSLCs were further sorted into CD34-negative and -positive cells. Compared with CD34-positive cells, CD34-negative MSLCs were significantly more sensitive to high inorganic phosphate (3.2 mM), calcifying easily in response. Furthermore, immunohistochemical staining showed that significantly higher numbers (～7-9-fold) of CD34-negative compared with CD34-positive MSLCs were localized in calcified aortic valve specimens obtained from calcified aortic stenosis patients. These results suggest that CD34-negative MSLCs are responsible for calcification of the aortic valve.

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“…AVICs from elderly individuals seem to be more easily calcified than cells from younger individuals, suggesting an effect of aging on the tendency to calcify (31). It has also been reported that these cells promote in vitro calcification through release of inflammatory cytokines (27,32). Interestingly, clear differences have been found between AVICs isolated from patients with and without calcification in terms of natural calcification ability and the calcification-promoter reaction against the inflammatory cytokine TNF-a.…”

Section: What Are the Cellular Origins In Calcification?mentioning

confidence: 96%

Recent Advances in Research on Human Aortic Valve Calcification

Furukawa

2014

J Pharmacol Sci

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Abstract. Aortic valve calcification can aggravate aortic stenoses, and it is a significant cause of sudden cardiac death. The increasing number of patients with age-related calcification is a problem in developed nations. However, the only treatment option currently available is highly invasive cardiac valve replacement. Therefore, clarification of the etiology of calcification is urgently needed to develop drug therapies and prevention methods. Recent studies have revealed that calcification is not a simple sedimentation of a mineral through a physicochemical phenomenon; various factors dynamically contribute to the mechanism. Further, we are finally beginning to understand the cellular origins of calcification, which had been unclear for a long time. Based on these findings that help to clarify potential drug targets, we expect to establish drug therapies that reduce the stress on patients. In this paper, I introduce the latest findings on cells that are most likely to contribute to calcification and on calcification-related factors that may lead to the development of drug therapies.

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Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis

Cited by 221 publications

References 29 publications

Pathogenesis of Calcific Aortic Valve Disease

Pathogenesis of Calcific Aortic Valve Disease

CD34-negative mesenchymal stem-like cells may act as the cellular origin of human aortic valve calcification

Recent Advances in Research on Human Aortic Valve Calcification

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