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Updated: Jan 11, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Reduced Circulating α-Klotho Levels Are Associated With Elevated Mortality and Arterial Calcifications of Aorta and
Elias Hellou1, Parvin Kalhor1, Ali Babaie1
1Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA.
Insights
Lower levels of the protein Klotho are linked to increased vascular calcification and higher mortality risk over 10 years. This suggests Klotho plays a role in aging blood vessels.
Area of Science:
- Gerontology
- Vascular Biology
- Biochemistry
Background:
- α-Klotho is a protein crucial for vascular health, with declining levels associated with aging-related vascular conditions.
- Reduced Klotho is linked to arterial stiffness, endothelial dysfunction, and vascular calcification.
Purpose of the Study:
- To investigate the relationship between circulating Klotho levels, aortoiliac calcification, endothelial progenitor cells, and long-term survival.
- To explore Klotho's role in the aging vasculature.
Main Methods:
- Retrospective cohort study of 148 participants.
- Calcification scored by blinded clinicians using computed tomography.
- Plasma Klotho measured by ELISA; endothelial progenitor cells quantified by flow cytometry; mortality data from death registry.
Main Results:
- Lower Klotho levels correlated with increased aortoiliac calcification (r=-0.315, P<0.01).
- Patients with low calcification had significantly higher Klotho levels (P<0.01).
- Low Klotho was independently associated with higher 10-year mortality (HR=3.056, P=0.014).
Conclusions:
- Decreased circulating Klotho levels are associated with greater aortoiliac calcification.
- Lower Klotho is a predictor of increased 10-year mortality.
- These findings support Klotho's significant role in vascular aging.
Background:
α-Klotho is a multifunctional protein implicated in vascular aging. Declining Klotho levels are associated with arterial stiffness, endothelial dysfunction, and vascular calcification. We investigated the associations between circulating klotho, aortoiliac calcification, endothelial progenitor cells, and 10-year survival.
Methods:
In this retrospective cohort, blinded clinicians scored calcification on computed tomography (0-10 scale: aorta 6 points, iliac 4 points). Plasma klotho was measured by ELISA; endothelial progenitor cell subsets were quantified via flow cytometry. Mortality data were obtained from the Minnesota Death Registry.
Results:
This study included 148 participants (mean age 72.4±9.6 years; 41% female). Median calcification score was 3 (interquartile range, 1-5). Patients with low calcification had higher Klotho levels (669 [567-841] versus 556 [457-678] pg/mL; P<0.01), with Klotho inversely correlated with calcification (r=-0.315, P<0.01). Stratified by calcification location and severity, the highest Klotho levels were seen in patients without aortic or iliac calcification (P=0.015). Over 10 years, low Klotho was independently associated with higher mortality (hazard ratio [HR], 3.056 [95% CI 1.288-7.878]; P=0.014). Klotho inversely correlated with mature osteocalcin-positive EPCs; B=-0.16 (95% CI, -0.29 to -0.02; P=0.027). Immunohistochemistry and immunofluorescence confirmed endothelial Klotho expression in internal mammary artery.
Conclusions:
Lower circulating Klotho levels are associated with increased aortoiliac calcification and higher 10-year mortality, supporting a role for Klotho in vascular aging.
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