Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells

Ikeda, Koji; Souma, Yuka; Akakabe, Yoshiki; Kitamura, Yoshihisa; Matsuo, Kiyonari; Shimoda, Yoshiaki; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Okigaki, Mitsuhiko; Matsubara, Hiroaki

doi:10.1016/j.bbrc.2012.07.045

Cited by 69 publications

(54 citation statements)

References 30 publications

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“…Several experimental and clinical studies have reported that inflammatory biomarkers such as tumor necrosis factor‐α, IL‐6, vascular adhesion molecule‐1, macrophage, and thrombomodulin were systemically or locally increased in the presence of ECF excess 39, 40. ECF excess directly induces a phenotype change in VSCMs and indirectly induces oxidative stress, which increases the production of bone morphogenetic protein 2 and endothelial cell–derived microparticles in endothelial cells, thereby enhancing the osteogenic signal acting on VSMCs 41, 42, 43…”

Section: Discussionmentioning

confidence: 99%

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

Park

Jhee

Yun

et al. 2018

JAHA

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BackgroundExtracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular disease, in patients with chronic kidney disease (CKD).Methods and ResultsA total of 1741 patients at all stages of pre‐dialysis CKD from the prospective observational cohort of CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center‐High Risk) were analyzed for the association between ECF status and CAC. ECF status was defined as extracellular water‐to‐total body water ratio (ECW/TBW) measured using bioelectrical impedance analysis. ECF excess was defined as ECW/TBW ≥0.390 or ≥0.400 depending on its severity. To define CAC, Agatston coronary artery calcium scores were measured. A total coronary artery calcium score of ≥400 was defined as CAC. The CKD stages were defined according to estimated glomerular filtration rate calculated using the CKD Epidemiology Collaboration equation. ECW/TBW and the proportion of ECF excess increased with progressing CKD stages. Multivariable logistic regression analyses showed that ECW/TBW was independently associated with CAC (per 0.01 increase of ECW/TBW, odds ratio 1.168, 95% confidence interval, 1.079–1.264, P<0.001). The adjusted R 2 for predicting higher coronary artery calcium scores and CAC significantly improved after ECW/TBW was added to conventional factors. This association was further confirmed by net reclassification and integrated discriminant improvements, sensitivity analysis, and subgroup analysis.Conclusions ECF status is independently associated with a high risk of CAC in patients with CKD.Study Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02003781.

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Section: Discussionmentioning

confidence: 99%

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

Park

Jhee

Yun

et al. 2018

JAHA

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“…Some studies have suggested that in procalcific conditions, SMCs produce IL-1β, or might signal to macrophages to increase IL-1β production. 12,16,23 These interactions between different cells and cytokines during plaque progression require further study so that treatments can be designed to treat all steps of plaque calcification.…”

Section: Apoementioning

confidence: 99%

“…[10][11][12][13] Tumor necrosis factor-α (TNF-α), released primarily by macrophages, has been established as a key cytokine; in addition to promoting apoptosis and accumulation of apoptotic bodies, TNF-α is also an activator of osteogenic programming in SMCs via the BMP-2 (bone morphogenetic protein 2), Msx2 (msh homeobox 2), Wnt signaling cascade. 7,14,15 Interleukin 1β (IL-1β) is another inflammatory cytokine reported to influence vascular calcification; however, the mechanisms involved are not completely clear and may be different from TNF-α.…”

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confidence: 99%

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Interleukin-1β Is a Key Biomarker and Mediator of Inflammatory Vascular Calcification

Shobeiri

Bendeck

2017

ATVB

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“…Inflammatory cytokines, including TNF-α, IL-1 and IL-6, are associated with increased cardiovascular calcification [97, 98], and in a cohort free of clinically apparent cardiovascular disease, high C-reactive protein levels were associated with coronary artery calcification in both men and women [99]. Inflammatory cytokines such as TNF-α and IL-1 may exert their effects by stimulating the release of BMP-2 [100-102] or may enhance BMP-2 activity by reducing the levels of its inhibitor, matrix Gla protein (MGP) [97]. TNF-α also enhances matrix vesicle secretion by VSMCs [89].…”

Section: Possible Mechanisms By Which Hmgb1 Promotes Cardiovascular Cmentioning

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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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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Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells

Cited by 69 publications

References 30 publications

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

Interleukin-1β Is a Key Biomarker and Mediator of Inflammatory Vascular Calcification

Roles of High Mobility Group Box 1 in Cardiovascular Calcification

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