Telomere Attrition and Clonal Hematopoiesis of Indeterminate Potential in Cardiovascular Disease

Area of Science:

• Cardiovascular Medicine
• Genetics
• Immunology

Background:

• Conventional cardiovascular disease (CVD) risk factors do not fully explain all CVD cases.
• Emerging evidence highlights the telomere-CHIP-atherosclerosis (TCA) axis in CVD development.
• Telomere attrition and clonal hematopoiesis of indeterminate potential (CHIP) are increasingly recognized in age-related CVD.

Purpose of the Study:

• To review recent research on telomere dynamics and CHIP.
• To elucidate the relationship between telomeres, CHIP, and atherosclerotic CVD.
• To understand the mechanisms underlying the TCA axis in CVD.

Main Methods:

• Literature review of recent studies on telomere biology, CHIP, and atherosclerosis.
• Analysis of epidemiological data and mechanistic insights.
• Synthesis of current understanding of the TCA axis.

Main Results:

• Telomere attrition is associated with CHIP, a condition common in elderly individuals.
• CHIP involves blood cell clones with mutations (e.g., DNMT3A, TET2, ASXL1), increasing risks for hematological cancer and atherosclerotic CVD.
• The TCA axis contributes to chronic inflammation and proinflammatory cytokine expression.

Conclusions:

• The TCA axis represents a significant, yet incompletely understood, pathway in CVD pathogenesis.
• Further research into the epidemiology and mechanisms of the TCA axis is warranted.
• Targeting pathways within the TCA axis may offer novel therapeutic strategies for CVD.