Vascular calcification: Molecular mechanisms and therapeutic interventions

Pan, Wei; Jie, Wei; Huang, Hui

doi:10.1002/mco2.200

Cited by 22 publications

(15 citation statements)

References 314 publications

(609 reference statements)

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“…Recently, various factors such as inflammatory cytokines, endoplasmic reticulum stress, autophagy dysfunction, mitochondrial dysfunction, and abnormal molecular signaling pathways have been reported to be involved in soft tissue calcification in addition to calcium and phosphorus concentrations. The mechanism of calcification of kidney grafts is unclear; however, it may be the result of the complex interaction of these multifactorial variables [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Persistent hyperparathyroidism after preemptive kidney transplantation

Toyoda¹,

Sato²,

Hasegawa³

et al. 2023

Clin Exp Nephrol

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Background Long-term dialysis vintage is a predictor of persistent hyperparathyroidism (HPT) after kidney transplantation (KTx). Recently, preemptive kidney transplantation (PKT) has increased. However, the incidence, predictors, and clinical implications of HPT after PKT are unclear. Here, we aimed to elucidate these considerations. Methods In this retrospective cohort study, we enrolled patients who underwent PKT between 2000 and 2016. Those who lost their graft within 1 year posttransplant were excluded. HPT was defined as an intact parathyroid hormone (PTH) level exceeding 80 pg/mL or hypercalcemia unexplained by causes other than HPT. Patients were divided into two groups based on the presence of HPT 1 year after PKT. The primary outcome was the predictors of HPT after PKT, and the secondary outcome was graft survival. Results Among the 340 consecutive patients who underwent PKT, 188 did not have HPT (HPT-free group) and 152 had HPT (HPT group). Multivariate logistic regression analysis revealed that pretransplant PTH level (P < 0.001; odds ratio [OR], 5.480; 95% confidence interval [CI], 2.070–14.50) and preoperative donor-estimated glomerular filtration rate (P = 0.033; OR, 0.978; 95% CI, 0.957–0.998) were independent predictors of HPT after PKT. Death-censored graft survival was significantly lower in the HPT group than that in the HPT-free group (90.4% vs. 96.4% at 10 years, P = 0.009). Conclusions Pretransplant PTH levels and donor kidney function were independent predictors of HPT after PKT. In addition, HPT was associated with worse graft outcomes even after PKT.

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Section: Discussionmentioning

confidence: 99%

Persistent hyperparathyroidism after preemptive kidney transplantation

Toyoda¹,

Sato²,

Hasegawa³

et al. 2023

Clin Exp Nephrol

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“…Osteo/chondrogenic transformed VSMCs secrete inflammatory cytokines like tumor necrosis factor alfa (TNF-alfa), IL-1beta, and IL-17A that in turn can also induce phenotypic VSMC transformation and consequent calcification via upregulation of Wnt/beta-catenin signaling pathway. Thus, a vicious cycle is formed which contributes to the deepening of VC [ 29 , 30 ] and the altered VSMC phenotype and the imbalance between activators and inhibitors of vascular calcification create a microenvironment favoring the initiation and progression of VC.…”

Section: Pathophysiology and Pathogenesis Of Vascular Calcificationmentioning

confidence: 99%

Extrahepatic Vitamin K-Dependent Gla-Proteins–Potential Cardiometabolic Biomarkers

Galunska,

Yotov,

Nikolova

et al. 2024

IJMS

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One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.

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“…In vascular calcification, calcium and phosphate deposition play a crucial role, leading to these multiple pathological processes. The chronic inflammation and increased expression of pro-inflammatory cytokines (e.g., Tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β, IL-6, cyclooxygenase [COX]-2, and inducible nitric oxide synthetase [iNOS]) initiate the osteogenic transdifferentiation of VSMCs into calcifying cells in the vasculature [ 81 ]. Bone morphogenetic proteins BMP signaling regulators such as MGP and BMP-binding endothelial regulator proteins serve a protective role in vascular calcification [ 82 ].…”

Section: Hypomagnesemia and Cardiovascular Mortalitymentioning

confidence: 99%

Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease

et al. 2023

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The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in advanced chronic kidney disease (CKD). In addition to nitrogen waste products, many pathological biochemical processes also play a role in vascular calcification in chronic kidney damage. Magnesium, a cation vital for the body, may substantially reduce cardiovascular diseases’ risk and progression. This narrative review aimed to address the relationship between hypomagnesemia and vascular calcification, which promotes further cardiovascular complications in diabetes, aging, and CKD. Articles with predefined keywords were searched for in the PubMed and Google Scholar databases with specific inclusion and exclusion criteria. We hypothesized that a decrease in serum magnesium levels contributes to increased vascular calcification and thereby increases cardiovascular mortality. In summary, based on existing evidence in the literature, it appears that simple and inexpensive oral magnesium supplementation may reduce the cardiovascular mortality of patients who are already severely affected by such diseases; in this context, the concept of ‘normal’ vs. ‘ideal’ serum magnesium levels should be carefully re-examined.

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Vascular calcification: Molecular mechanisms and therapeutic interventions

Cited by 22 publications

References 314 publications

Persistent hyperparathyroidism after preemptive kidney transplantation

Persistent hyperparathyroidism after preemptive kidney transplantation

Extrahepatic Vitamin K-Dependent Gla-Proteins–Potential Cardiometabolic Biomarkers

Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease

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