Stanniocalcin-2 overexpression reduces atherosclerosis in hypercholesterolemic mice

Area of Science:

• Vascular Biology
• Biochemistry
• Cardiovascular Research

Background:

• Pregnancy-associated plasma protein-A (PAPP-A) is implicated in atherosclerosis due to its role in insulin-like growth factor signaling.
• Stanniocalcin-2 (STC2) is a newly identified inhibitor of PAPP-A, with its role in vascular disease previously unestablished.

Purpose of the Study:

• To investigate the interaction between PAPP-A and STC2 within the artery wall.
• To explore the potential of STC2 as a local regulator of vascular disease.

Main Methods:

• Cultured human aortic smooth muscle cells were used to study PAPP-A and STC2 complex formation.
• Immunohistochemistry was employed to detect PAPP-A and STC2 in human atherosclerotic plaques.
• Adeno-associated virus-mediated STC2 expression was used in apolipoprotein E-deficient mice to assess atherosclerosis development.

Main Results:

• PAPP-A forms an inactive complex with STC2 when secreted by smooth muscle cells.
• Both complexed and uncomplexed PAPP-A, along with STC2, are present in human atherosclerotic lesions.
• Increased STC2 levels significantly reduced atherosclerosis progression by 47% in a mouse model.

Conclusions:

• This research establishes STC2's involvement in regulating PAPP-A activity during atherosclerosis development.
• Targeting the PAPP-A/STC2 balance offers a potential therapeutic strategy for inhibiting lesion development.