Wnt Pathway Gene Expression Is Associated With Arterial Stiffness

Area of Science:

• Cardiovascular biology
• Molecular genetics
• Vascular health

Background:

• The Wnt pathway is implicated in cardiovascular processes like fibrosis and atherosclerosis in animal models.
• Human research on the Wnt pathway's role in cardiovascular health, particularly arterial stiffness, is limited.
• African ancestry men are at increased risk for hypertensive vascular disease.

Purpose of the Study:

• To investigate the association between peripheral blood Wnt pathway gene expression and arterial stiffness in healthy African ancestry men.
• To identify specific Wnt pathway genes linked to arterial stiffness in this population.

Main Methods:

• Gene expression of 43 Wnt pathway genes was measured in peripheral blood from 369 African ancestry men.
• Arterial stiffness was assessed using brachial-ankle pulse-wave velocity.
• Linear regression models were used to analyze associations between gene expression and pulse-wave velocity, adjusting for covariates.

Main Results:

• Fourteen Wnt genes showed detectable expression.
• Expression of Adenomatous polyposis coli regulator of Wnt signaling pathway (APC), glycogen synthase kinase 3β (GSK3B), and transcription factor 4 (TCF4) were significantly associated with arterial stiffness.
• APC and TCF4 expression remained independently associated with arterial stiffness, each explaining approximately 3% of the variance.

Conclusions:

• This study establishes a novel association between in vivo expression of Wnt pathway genes APC and TCF4 and arterial stiffness.
• These findings suggest a potential molecular link between Wnt signaling and vascular health in African ancestry men.
• Further research may explore therapeutic targets within the Wnt pathway for managing arterial stiffness.