Cell-matrix mechanics and pattern formation in inflammatory cardiovascular calcification

Hsu, Jeffrey J.; Lim, Jina; Tintut, Yin; Demer, Linda L.

doi:10.1136/heartjnl-2016-309667

Cited by 45 publications

(37 citation statements)

References 70 publications

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“…The entire cardiovascular system is vulnerable to pathological calcification [1], and vascular disease, such as atherosclerosis, arteriosclerosis and diabetic vasculopathy, is frequently complicated by calcification [2]. Calcification in arteries can be widespread, and the prevalence increases with age.…”

Section: Introductionmentioning

confidence: 99%

“…Another common site of calcification is the aortic valve, termed calcific aortic valvular disease (CAVD), which has severe consequences. Approximately 40% of people over the age of 70 years have mild calcification of the aortic valve, with over 10% having severe calcification [1]. Lastly, calcification of arterioles of the skin and other organs can lead to localized infarction and ischemia, including ischemic bowel and calciphylaxis [4].…”

Section: Introductionmentioning

confidence: 99%

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Roles of High Mobility Group Box 1 in Cardiovascular Calcification

Chen¹,

Wang²,

Chen³

et al. 2017

Cell Physiol Biochem

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Calcific disease of the cardiovascular system, including atherosclerotic calcification, medial calcification in diabetes and calcific aortic valve disease, is an important risk factor for many adverse cardiovascular events such as ischemic cardiac events and subsequent mortality. Although cardiovascular calcification has long been considered to be a passive degenerative occurrence, it is now recognized as an active and highly regulated process that involves osteochondrogenic differentiation, apoptosis and extracellular vesicle release. Nonetheless, despite numerous studies on the pathogenesis of cardiovascular calcification, the underlying mechanisms remain poorly understood. High mobility group box 1 (HMGB1), a nuclear protein bound to chromatin in almost all eukaryotic cells, acts as a damage-associated molecular pattern (DAMP) when released into the extracellular space upon cell activation, injury or death. Moreover, HMGB1 also functions as a bone-active cytokine participating in bone remodeling and ectopic calcification pathogenesis. However, studies on the roles of HMGB1 in promoting cardiovascular calcification are limited to date, and the mechanisms involved are still unclear. In this review, we summarize recent studies investigating the mechanism of cardiovascular calcification and discuss multiple roles of HMGB1 in its development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of High Mobility Group Box 1 in Cardiovascular Calcification

Chen¹,

Wang²,

Chen³

et al. 2017

Cell Physiol Biochem

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“…In an established mouse model of acquired AS, valve interstitial cells undergo transdifferentiation into myofibroblasts, which express α‐SMA and produce interstitial collagen 16. Myofibroblasts may then transdifferentiate further into osteoblast‐like cells, which produce matrix calcification 24. Similar processes occur in diseased human valves, in which α‐SMA and calcification colocalize 25.…”

Section: Discussionmentioning

confidence: 98%

Discovery of an Experimental Model of Unicuspid Aortic Valve

Weiß

Chu

Brooks

et al. 2018

JAHA

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BackgroundThe epithelial growth factor receptor family of tyrosine kinases modulates embryonic formation of semilunar valves. We hypothesized that mice heterozygous for a dominant loss‐of‐function mutation in epithelial growth factor receptor, which are Egfr Vel/+ mice, would develop anomalous aortic valves, valve dysfunction, and valvular cardiomyopathy.Methods and ResultsAortic valves from Egfr Vel/+ mice and control mice were examined by light microscopy at 2.5 to 4 months of age. Additional Egfr Vel/+ and control mice underwent echocardiography at 2.5, 4.5, 8, and 12 months of age, followed by histologic examination. In young mice, microscopy revealed anatomic anomalies in 79% of Egfr Vel/+ aortic valves, which resembled human unicuspid aortic valves. Anomalies were not observed in control mice. At 12 months of age, histologic architecture was grossly distorted in Egfr Vel/+ aortic valves. Echocardiography detected moderate or severe aortic regurgitation, or aortic stenosis was present in 38% of Egfr Vel/+ mice at 2.5 months of age (N=24) and in 74% by 8 months of age. Left ventricular enlargement, hypertrophy, and reversion to a fetal myocardial gene expression program occurred in Egfr Vel/+ mice with aortic valve dysfunction, but not in Egfr Vel/+ mice with near‐normal aortic valve function. Myocardial fibrosis was minimal or absent in all groups.ConclusionsA new mouse model uniquely recapitulates salient functional, structural, and histologic features of human unicuspid aortic valve disease, which are phenotypically distinct from other forms of congenital aortic valve disease. The new model may be useful for elucidating mechanisms by which congenitally anomalous aortic valves become critically dysfunctional.

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“…Vascular cells, like bone cells, interact with their matrix substrate through molecular signals and biomechanical signals to control pathological calcification of the artery wall and cardiac valves (4). The present study by Pallai et al also showed involvement of cellmatrix mechanics in pathological heart calcificationthat CFs express ENPP1, and ENPP1-generated PPi in heart increases mineralization via hydrolysis of PPi to generate Pi by tissue non-specific alkaline phosphatase (TANP) and subsequent calcium hydroxyapatite formation in extracellular matrix to develop post-injury cardiac calcification.…”

Section: Editorialmentioning

confidence: 99%

“…Any abnormality of calcium metabolism can lead to metastatic myocardial calcification, including chronic renal failure, bone destruction or increased bone turnover, hyperparathyroidism, and vitamin D-related disorders. Calcification of the cardiovascular system, such as aortic valve and vascular calcification, has important clinical significance (4). Myocardial calcification is an unusual form of soft tissue calcification characterized by abnormal calcific accumulation within the heart muscle which can occur in the absence of calcification of vessels, valves, or other organs (5).…”

mentioning

confidence: 99%