The Pharmacological Effect and Mechanism of Lanthanum Hydroxide on
Vascular Calcification Caused by Chronic Renal Failure Hyperphosphatemia
Abstract
Background and Purpose: To investigate the treatment and mechanism of
lanthanum hydroxide on hyperphosphate-induced vascular calcification in
chronic renal failure. Experimental Approach: Develop a rat model of CKD
hyperphosphatemia. Rats were randomly allocated to the model, lanthanum
hydroxide, lanthanum carbonate, Calcium carbonate groups. Determination
of serum biochemical indicators and the determination of pathological
analysis of kidney tissue, Von Kossa staining and CT scan on the aortic
vessels. The proteomic analysis of aortic tissue in Vivo. A calcified
VSMCs model was established. The calcium content and ALP activity were
measured. RT-PCR measures the mRNA expression level of SM22α, Runx2,
BMP-2 and TRAF6. Western Blot measures the protein expression level of
SM22α, Runx2, BMP-2, TRAF6 and NF-κB. Key Results: Through the detection
of serum biochemical indicators and pathological analysis of kidney
tissue, it can be summaryed that lanthanum hydroxide has the effect of
delaying the progression of renal failure and protecting renal function.
We found that the administration of lanthanum hydroxide delayed the
development of vascular calcification induced by hyperphosphatemia in
CKD. It can be concluded that lanthanum hydroxide may affect vascular
calcification through the NF-κB pathway. In cultured VSMCs, treatment
with Lanthanum chloride (LaCl3) blunted phosphate-induced calcification,
osteo-/chondrogenic signaling, and NF-κB activation. Lanthanum hydroxide
significantly reduces the expression of Runx2, BMP-2, TRAF6 and NF-κB.
Conclusion and Implications: Lanthanum hydroxide has a protective effect
on the kidneys, and can delay the development of vascular calcification
by reducing serum phosphorus concentration. KEYWORDS: Lanthanum
hydroxide, vascular calcification, chronic renal failure,
hyperphosphatemia, pharmacological effect, mechanism