Plaque Calcification

Akers, Emma; Nicholls, Stephen J.; Bartolo, Belinda A. Di

doi:10.1161/atvbaha.119.311574

Cited by 54 publications

(30 citation statements)

References 139 publications

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“…Atherosclerotic calcification in an advanced lesion may increase risk of cardiovascular events [44,45]. SMCs play critical roles in mediating intimal calcification by undergoing differentiation to osteoblast-like cells via increasing expression of calcification regulators, RUXN2, and BMP2 [46,47]. RUNX2, a decisive factor and early marker of SMC osteogenic transition and calcification that can be induced by BMP2, increases the expression of multiple osteogenic genes including collagen I, osteopontin, bone sialoprotein, and osteocalcin [11,48].…”

Section: Discussionmentioning

confidence: 99%

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

et al. 2021

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Vascular calcification is strongly associated with atherosclerotic plaque burden and plaque instability. The activation of extracellular signal-regulated kinase 1/2 (ERK1/2) increases runt related transcription factor 2 (RUNX2) expression to promote vascular calcification. Procyanidin B2 (PB2), a potent antioxidant, can inhibit ERK1/2 activation in human aortic smooth muscle cells (HASMCs). However, the effects and involved mechanisms of PB2 on atherosclerotic calcification remain unknown. In current study, we fed apoE-deficient (apoE−/−) mice a high-fat diet (HFD) while treating the animals with PB2 for 18 weeks. At the end of the study, we collected blood and aorta samples to determine atherosclerosis and vascular calcification. We found PB2 treatment decreased lesions in en face aorta, thoracic, and abdominal aortas by 21.4, 24.6, and 33.5%, respectively, and reduced sinus lesions in the aortic root by 17.1%. PB2 also increased α-smooth muscle actin expression and collagen content in lesion areas. In the aortic root, PB2 reduced atherosclerotic calcification areas by 75.8%. In vitro, PB2 inhibited inorganic phosphate-induced osteogenesis in HASMCs and aortic rings. Mechanistically, the expression of bone morphogenetic protein 2 and RUNX2 were markedly downregulated by PB2 treatment. Additionally, PB2 inhibited ERK1/2 phosphorylation in the aortic root plaques of apoE−/− mice and calcified HASMCs. Reciprocally, the activation of ERK1/2 phosphorylation by C2-MEK1-mut or epidermal growth factor can partially restore the PB2-inhibited RUNX2 expression or HASMC calcification. In conclusion, our study demonstrates that PB2 inhibits vascular calcification through the inactivation of the ERK1/2-RUNX2 pathway. Our study also suggests that PB2 can be a potential option for vascular calcification treatment.

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Section: Discussionmentioning

confidence: 99%

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

et al. 2021

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“…Отправной точкой начала кальцификации может служить отложение микроскопических гранул кальция на останках погибших клеток и некротического ядра АСБ. Другими важными аспектами кальцификации являются остеогенная дифференцировка сосудистых гладкомышечных клеток и высокая активность генерирующих фосфаты ферментов, в частности, щелочной фосфатазы [14]. Можно предположить, что разрастание сосудов неоинтимы в области вновь образованного кальцификата способствует постоянной доставке минеральных ионов и биоактивных веществ, необходимых для формирования кальцификата.…”

Section: Discussionunclassified

Regularities of plaque stabilization in various scenarios of neointimal calcification and vascularization

et al. 2021

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Aim. To study the relationships between phenotypes of extracranial arteries' plaques (stable/unstable), their calcification and its causes, in particular, vascularization.Material and methods. The study included 88 patients: patients (n=44) with ischemic stroke and those (n=44) with chronic brain ischemia. In all subjects, the parameters of systemic mineral homeostasis were assessed (total and ionized calcium, phosphate, total protein, albumin, and calcification propensity). Atherosclerotic plaques have been obtained during carotid endarterectomy, fixed in formalin, postfixed in 1% osmium tetroxide, stained in 2% osmium tetroxide, dehydrated in ascending ethanol series and acetone, stained with 2% alcoholic uranyl acetate and embedded into epoxy resin with its further polymerization. Epoxy resin blocks were grinded, polished, counterstained with Reynolds' lead citrate and sputter coated with carbon. Sample visualization was performed employing backscattered scanning electron microscopy. Number and area of calcium deposits and neointimal vessels were quantified using ImageJ. Statistical analysis was carried out using Mann-Whitney U-test and Spearman's rank correlation coefficient.Results. It was found that area of neointimal calcification, but not number of calcium deposits, was associated with the stable plaque phenotype. The stabilizing effect of calcification was manifested in retarding stenosis associated with plaque rupture and stroke. Calcification extent directly correlated with total and local plaque vascularization, which have been associated with unstable and stable plaque phenotype, respectively. In addition, plaque calcification negatively correlated with total protein and albumin, thereby reflecting the impaired systemic mineral homeostasis.Conclusion. Atherosclerotic plaque calcification and active local vascularization reduce stenosis extent and stabilize plaque. In contrast, total plaque calcification contributes to the atherosclerosis progression and promotes major acute cardiovascular events.

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“…Arteriosclerotic calcification, commonly regarded as a latestage complication of atherosclerotic plaques, is an active process under tight regulations and is an independent predictor of cardiovascular morbidity and mortality (80). Although calcification of atherosclerosis plaques used to be considered unregulated and a passive deposition of calcium in the arterial wall, it is now well-recognized as a complex pathophysiological phenomenon resembling intramembranous ossification (81). YAP can interact with various factors involved in osteoblast development and maturation, such as Runx2 (82), bone morphogenic protein-2 (BMP-2) (83), and β-catenin (84).…”

Section: Yap In Atherosclerotic Complications Yap and Atherosclerotic Calcificationmentioning

confidence: 99%

Yes-Associated Protein in Atherosclerosis and Related Complications: A Potential Therapeutic Target That Requires Further Exploration

Sun

et al. 2021

Front. Cardiovasc. Med.

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Atherosclerosis and its complications diseases remain leading causes of cardiovascular morbidity and mortality, bringing a massive burden on public health worldwide. Atherosclerosis is recognized as chronic inflammation, and involves several highly correlated processes, including lipid metabolism dysfunction, endothelial cell dysfunction, inflammation, oxidative stress, vascular smooth muscle cell activation, platelet activation, thrombosis, altered matrix metabolism, and vascular remodeling. Within the past few decades, accumulating evidence has shown that the Yes-associated protein (YAP), the major effector of the Hippo pathway, can play a crucial role in pathogenesis and development of atherosclerosis. Activation of YAP-related pathways, which are induced by alerting flow pattern and matrix stiffness among others, can regulate processes including vascular endothelial cell dysfunction, monocyte infiltration, and smooth muscle cell migration, which contribute to atherosclerotic lesion formation. Further, YAP potentially modulates atherosclerotic complications such as vascular calcification and intraplaque hemorrhage, which require further investigation. Here, we summarized the relevant literature to outline current findings detailing the relationship between of YAP and atherosclerosis and highlight areas for future research.

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Plaque Calcification

Cited by 54 publications

References 139 publications

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

Regularities of plaque stabilization in various scenarios of neointimal calcification and vascularization

Yes-Associated Protein in Atherosclerosis and Related Complications: A Potential Therapeutic Target That Requires Further Exploration

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