Francesca Elli

University of Milan, Milano, Lombardy, Italy

Are you Francesca Elli?

Claim your profile

Publications (6)15.56 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: High serum phosphate (Pi) levels represent a major issue in dialysis patients, because associate with secondary hyperparathyroidism, vascular calcification (VC), and cardiovascular outcomes. In this population, calcimimetics are used to control secondary hyperparathyroidism, hyperphosphatemia, and, more recently, to delay the progression of VC. The aim of this in vitro study was to investigate the direct effects of the calcimimetic calindol on the progression of high Pi-induced VC. Methods: Rat vascular smooth muscle cells (VSMCs) were incubated with high Pi concentrations, and the effects of calindol were investigated on vascular calcium deposition and VSMC osteoblastic differentiation. Results: Calindol inhibited calcium deposition concentration-dependently with a maximal inhibition of 64.0 ± 5.2% achieved at 100 nM. Furthermore, calindol was able to partially prevent the high Pi-induced bone morphogenic protein 2 (BMP-2) expression upregulation (32.4 ± 4.6% of inhibition; p < 0.01). Interestingly, the pretreatment with calindol enhanced the matrix Gla protein (MGP) gene expression significantly, compared to high Pi-treated cells (40.2 ± 6.6% of increase, p < 0.01). Conclusions: In conclusion, we demonstrated that the calcimimetic calindol prevents high Pi-induced VC by affecting osteoblastic differentiation in vitro. In particular, the inhibitory effect of calindol on VC is probably due to its stimulatory role on the calcium-sensing receptor, leading to an increase in the synthesis of MGP by VSMCs.
    Nephron Experimental Nephrology 03/2013; 122(3-4):75-82. · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vascular calcification (VC) represents a major cardiovascular risk factor in chronic kidney disease patients. High phosphate (Pi) levels are strongly associated with VC in this population. Therefore, Pi binders are commonly used to control high Pi levels. The aim of this work was to study the mechanism of action of lanthanum chloride (LaCl(3)) on the progression of Pi-induced VC through its direct effect on vascular smooth muscle cells (VSMCs) in vitro. High Pi induced VSCM Ca deposition. We evaluated the action of LaCl(3), compared to gadolinium chloride (GdCl(3)), and found different effects on the modulation of VSMC lineage markers, such as α-actin and SM22α. In fact, only LaCl(3) preserved the expression of both VSMC lineage markers compared to high Pi-treated cells. Interestingly, both LaCl(3) and GdCl(3) reduced the high Pi-induced elevations of bone morphogenic protein 2 mRNA expression, with no reduction of the high core binding factor-alpha 1 mRNA levels observed in calcified VSMCs. Furthermore, we also found that only LaCl(3) completely prevented the matrix GLA protein mRNA levels and osteonectin protein expression elevations induced by high Pi compared to GdCl(3). Finally, LaCl(3), in contrast to GdCl(3), prevented the high Pi-induced downregulation of Axl, a membrane tyrosine kinase receptor involved in apoptosis. Thus, our results suggest that LaCl(3) prevents VC by preserving VSMC lineage markers and by decreasing high Pi-induced osteoblastic differentiation.
    Calcified Tissue International 02/2013; · 2.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2012; · 3.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 05/2012; 22(7):547-52. · 3.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphate (Pi)-binders are commonly used in dialysis patients to control high Pi levels, that associated with vascular calcification (VC). The aim of this study was to investigate the effects of lanthanum chloride (LaCl(3)) on the progression of high Pi-induced VC, in rat vascular smooth muscle cells (VSMCs). Pi-induced Ca deposition was inhibited by LaCl(3), with a maximal effect at 100μM (59.0±2.5% inhibition). Furthermore, we studied the effects on VC of calcium sensing receptor (CaSR) agonists. Gadolinium chloride, neomycin, spermine, and the calcimimetic calindol significantly inhibited Pi-induced VC (55.9±2.2%, 37.3±4.7%, 30.2±5.7%, and 63.8±5.7%, respectively). To investigate the hypothesis that LaCl(3) reduces the progression of VC by interacting with the CaSR, we performed a concentration-response curve of LaCl(3) in presence of a sub-effective concentration of calindol (10nM). Interestingly, this curve was shifted to the left (IC(50) 9.6±2.6μM), compared to the curve in the presence of LaCl(3) alone (IC(50) 19.0±4.8μM). In conclusion, we demonstrated that lanthanum chloride effectively reduces the progression of high phosphate-induced vascular calcification. In addition, LaCl(3) cooperates with the calcimimetic calindol in decreasing Ca deposition in this in vitro model. These results suggest the potential role of lanthanum in the treatment of VC induced by high Pi.
    Biochemical and Biophysical Research Communications 02/2012; 418(4):770-3. · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic kidney disease (CKD) is characterized by phosphorus retention and, in more advanced stages, by high serum phosphorus (P) levels. During the last decade, it has been elucidated the central role of P in the pathogenesis of CKD mineral bone disorder (CKD-MBD), determining both renal osteodystrophy and cardiovascular disease. Unfortunately, at least one third of patients on chronic dialysis have high serum P levels, with a consequent higher serum PTH levels, commonly associated with vitamin D deficiency, increased vascular calcification and the highest ratios of morbidity and mortality. In patients with CKD stage 5 on dialysis, therapeutic approaches to reduce serum P levels should include restriction of dietary phosphate intake, optimal dialysis treatment, and use of P binders. In this context, the use of P binders appears to be an essential treatment to control P overload in CKD patients. In this review, we analyzed the use of calcium-based and calcium-free P binders in peritoneal dialysis patients.
    Contributions to nephrology 01/2012; 178:116-23. · 1.49 Impact Factor