Klotho: a link between cardiovascular and non-cardiovascular mortality

Area of Science:

• Endocrinology
• Gerontology
• Cardiovascular Medicine

Background:

• Klotho is a membrane protein crucial for fibroblast growth factor 23 (FGF23) signaling in the kidney and parathyroid glands.
• Its cleaved form in circulation exhibits endocrine functions, including anti-inflammatory and antioxidative activities, potentially mediating anti-aging effects.
• Klotho modulates mineral metabolism and FGF23 activity, mitigating cardiovascular risks associated with these processes.

Discussion:

• Circulating Klotho levels correlate with cardiovascular conditions like myocardial hypertrophy, coronary artery disease, and stroke.
• Klotho may play a role in salt-sensitive hypertension pathogenesis, partly mediated by inflammatory cytokines.
• Reduced Klotho levels are observed in chronic kidney disease (CKD) patients, impacting tissue and blood concentrations.

Key Insights:

• Higher serum Klotho levels are associated with reduced cardiovascular and non-cardiovascular mortality.
• Specific Klotho genetic polymorphisms, notably rs9536314, influence clinical associations and predict cardiovascular risk.
• Klotho and its polymorphisms may link inflammation, salt sensitivity, hypertension, and mortality, particularly in CKD.

Outlook:

• Investigating Klotho's therapeutic potential for cardiovascular diseases and age-related conditions.
• Further research into the mechanisms underlying Klotho's role in hypertension and inflammation.
• Developing strategies to modulate Klotho levels or activity in conditions like CKD for improved patient outcomes.