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Updated: Jul 11, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Humoral and cellular factors inhibit phosphate-induced vascular calcification during the growth period
Yuki Kamei1,2, Yosuke Okumura1, Yuichiro Adachi1
1Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Insights
Growing mice resist vascular calcification due to high fetuin-A and low tissue-nonspecific alkaline phosphatase (TNAP) levels. This suggests a protective defense system against high phosphate levels during development.
Area of Science:
- Cardiovascular Biology
- Nephrology
- Developmental Biology
Background:
- Hyperphosphatemia is a key risk factor for cardiovascular disease and mortality in chronic kidney disease (CKD) patients.
- Elevated inorganic phosphate (Pi) induces vascular calcification, but mechanisms remain unclear.
- Growing individuals have high Pi levels without typical vascular calcification, suggesting developmental resistance.
Purpose of the Study:
- To investigate the existence and mechanisms of a defense system against phosphate-induced vascular calcification during development.
- To compare the calcification propensity of young versus adult mouse serum and aortas in response to high phosphate.
Main Methods:
- Comparison of calcification propensity in young (3-week-old) and adult (10-month-old) mouse serum.
- In vitro culture of young and adult mouse aortas in high inorganic phosphate (Pi) medium.
- Analysis of mRNA levels for tissue-nonspecific alkaline phosphatase (TNAP) in cultured aortas.
Main Results:
- Young serum exhibited significantly lower calcification propensity than adult serum, potentially due to higher fetuin-A levels.
- Adult aortas showed obvious calcification in high Pi medium, while young aortas did not.
- High Pi medium increased TNAP mRNA levels only in adult aortas, suggesting suppressed pyrophosphate degradation in young aortas.
Conclusions:
- The aorta in growing mice is resistant to Pi-induced vascular calcification.
- This resistance is attributed to high serum fetuin-A levels and suppressed TNAP expression during development.
- Findings highlight a protective mechanism against vascular calcification in younger individuals.
Abstract:
Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels of extracellular inorganic phosphate (Pi) are known to directly induce vascular calcification, but the detailed underlying mechanism has not been clarified. Although serum Pi levels during the growth period are as high as those observed in hyperphosphatemia in adult CKD, vascular calcification does not usually occur during growth. Here, we have examined whether the defence system against Pi-induced vascular calcification can exist during the growth period using mice model. We found that calcification propensity of young serum (aged 3 weeks) was significantly lower than that of adult serum (10 months), possibly due to high fetuin-A levels. In addition, when the aorta was cultured in high Pi medium in vitro, obvious calcification was observed in the adult aorta but not in the young aorta. Furthermore, culture in high Pi medium increased the mRNA level of tissue-nonspecific alkaline phosphatase (TNAP), which degrades pyrophosphate, only in the adult aorta. Collectively, our findings indicate that the aorta in growing mouse may be resistant to Pi-induced vascular calcification via a mechanism in which high serum fetuin-A levels and suppressed TNAP expression.
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