Iron citrate reduces high phosphate-induced vascular calcification by inhibiting apoptosis

Ciceri, Paola; Elli, Francesca; Braidotti, Paola; Falleni, Monica; Tosi, Delfina; Bulfamante, Gaetano; Block, Geoffrey A.; Cozzolino, Mario

doi:10.1016/j.atherosclerosis.2016.09.071

Cited by 48 publications

(51 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance, phosphate inhibits AKT phosphorylation in VSMCs [ 56 , 100 , 183 ], while activation of the PI3K/AKT pathway may prevent phosphate-induced apoptosis of VSMCs [ 56 ]. Similarly, vitamin K2 [ 182 ], iron citrate [ 185 ], estrogens [ 186 ], testosterone [ 187 ], α-lipoic acid [ 188 ], or statins [ 183 , 184 ] inhibit phosphate-induced VSMCs apoptosis by restoring the Gas6-dependent anti-apoptotic pathway, effects leading to a reduction in VSMC calcification [ 54 , 55 ]. A key up-stream regulator of Gas6 expression in VSMCs is the AMP-activated protein kinase (AMPK) [ 189 , 190 ].…”

Section: Signaling Pathways Regulating Vsmcs Calcification During Higmentioning

confidence: 99%

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

Voelkl

Läng

Eckardt

et al. 2019

Cell. Mol. Life Sci.

139

202

View full text Add to dashboard Cite

Medial vascular calcification has emerged as a putative key factor contributing to the excessive cardiovascular mortality of patients with chronic kidney disease (CKD). Hyperphosphatemia is considered a decisive determinant of vascular calcification in CKD. A critical role in initiation and progression of vascular calcification during elevated phosphate conditions is attributed to vascular smooth muscle cells (VSMCs), which are able to change their phenotype into osteo-/chondroblasts-like cells. These transdifferentiated VSMCs actively promote calcification in the medial layer of the arteries by producing a local pro-calcifying environment as well as nidus sites for precipitation of calcium and phosphate and growth of calcium phosphate crystals. Elevated extracellular phosphate induces osteo-/chondrogenic transdifferentiation of VSMCs through complex intracellular signaling pathways, which are still incompletely understood. The present review addresses critical intracellular pathways controlling osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification during hyperphosphatemia. Elucidating these pathways holds a significant promise to open novel therapeutic opportunities counteracting the progression of vascular calcification in CKD.

show abstract

Section: Signaling Pathways Regulating Vsmcs Calcification During Higmentioning

confidence: 99%

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

Voelkl

Läng

Eckardt

et al. 2019

Cell. Mol. Life Sci.

139

202

View full text Add to dashboard Cite

show abstract

“…Emerging evidence indicate that autophagy also regulates extracellular matrix homeostasis and mitigates VC formation [71, 72]. In the setting of hyperphosphatemia, autophagy may be an endogenous protective mechanism counteracting phosphate-induced VC.…”

Section: Other Evidence Of Cellular Interactions In Vcmentioning

confidence: 99%

A novel role of cellular interactions in vascular calcification

et al. 2017

View full text Add to dashboard Cite

A series of clinical trials have confirmed the correlation between vascular calcification (VC) and cardiovascular events and mortality. However, current treatments have little effects on the regression of VC. Potent and illustrative mechanisms have been proven to exist in both bone metabolism and VC, indicating that these two processes share similarities in onset and progression. Multiple osteoblast-like cells and signaling pathways are involved in the process of VC. In this review, we summarized the roles of different osteoblast-like cells and we emphasized on how they communicated and interacted with each other using different signaling pathways. Further studies are needed to uncover the underlying mechanisms and to provide novel therapies for VC.

show abstract

“…Therefore, iron‐based phosphate binders such as ferric citrate are promising as an anticalcific agent. In fact, ferric citrate is reported to reduce high‐phosphate level‐induced vascular calcification in vitro . The mechanism includes inhibition of apoptosis and activation of impaired autophagy.…”

Section: Potential Solutions For Vascular Calcification In the Futurementioning

confidence: 99%

“…In fact, ferric citrate is reported to reduce high-phosphate level-induced vascular calcification in vitro. 29 The mechanism includes inhibition of apoptosis and activation of impaired autophagy. Another phosphate binder, sucroferric oxyhydroxide (PA-21), also replenishes iron in dialysis patients, especially those with iron deficiency.…”

Section: Iron-based Phosphate Bindersmentioning

confidence: 99%

Mineral and bone disorders in conventional hemodialysis: Challenges and solutions

Hamano

2018

Seminars in Dialysis

View full text Add to dashboard Cite

Despite the advent of cinacalcet and noncalcium-containing phosphate binders, controlling the progression of vascular calcification (VC) is still challenging. Recent reports demonstrate that carbamylation driven by high urea concentration aggravates VC, suggesting the importance of adequate dialysis in retarding its progression. Theoretically, other promising measures include the use of iron-based phosphate binders, vitamin K, and magnesium supplements, which should be investigated in future randomized controlled trials (RCTs), ideally with hard outcomes. While incidence of hip fracture in patients on dialysis is decreasing in the United States and Japan (possibly owing to better control of PTH levels by cinacalcet) it remains much higher than that in the general population. Many drugs used in the treatment of osteoporosis, including bisphosphonate, raloxifene, denosumab, and teriparatide can, under specific conditions, increase bone mineral density (BMD), which is associated with a lower fracture rate. However, the efficacy of these drugs in reducing the fracture rate remains to be proven in hemodialysis (HD) patients, given their adverse effects such as severe hypocalcemia and resultant worsening of secondary hyperparathyroidism. Some clinical studies have shown that cinacalcet, lanthanum carbonate, and sevelamer reduce mortality in elderly patients on HD, suggesting the benefits of reducing PTH and serum phosphate levels. However, the target ranges of PTH and phosphate levels are based solely on observational studies. This is also the case when treating low PTH levels by decreasing vitamin D or calcium load. RCTs with hard clinical endpoints comparing different targets are necessary in the future.

show abstract

Iron citrate reduces high phosphate-induced vascular calcification by inhibiting apoptosis

Cited by 48 publications

References 39 publications

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

A novel role of cellular interactions in vascular calcification

Mineral and bone disorders in conventional hemodialysis: Challenges and solutions

Contact Info

Product

Resources

About