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Pregnancy-Associated Plasma Protein-A Accelerates Atherosclerosis by Regulating Reverse Cholesterol Transport and

Shi-Lin Tang1, Zhen-Wang Zhao2, Shang-Ming Liu1

  • 1Department of Intensive Care Unit, the First Affiliated Hospital of University of South China.

Circulation Journal : Official Journal of the Japanese Circulation Society
|January 22, 2019
PubMed

Insights

Pregnancy-associated plasma protein-A (PAPP-A) promotes atherosclerosis by impairing reverse cholesterol transport and increasing inflammation. Reducing PAPP-A levels in mice significantly alleviated atherosclerotic lesions and improved cholesterol metabolism.

Area of Science:

  • Cardiovascular Biology
  • Atherosclerosis Research
  • Molecular Medicine

Background:

  • Pregnancy-associated plasma protein-A (PAPP-A) is increasingly implicated in atherosclerosis pathogenesis.
  • Understanding PAPP-A's role in reverse cholesterol transport (RCT) and inflammation is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the mechanistic role of PAPP-A in reverse cholesterol transport (RCT) and inflammation during atherosclerosis development.
  • To evaluate the therapeutic potential of targeting PAPP-A in a mouse model of atherosclerosis.

Main Methods:

  • Apolipoprotein E knockout (apoE-/-) mice were treated with PAPP-A shRNA to silence PAPP-A expression.
  • Atherosclerotic lesion development was assessed using Oil Red O, HE, and Masson staining.
  • Changes in lipid metabolism, inflammatory markers, and signaling pathways (PI3K/Akt, NF-κB) were analyzed in aortic and peritoneal macrophages.

Main Results:

  • PAPP-A knockdown significantly reduced lipid accumulation and atherosclerotic lesion formation in the aorta.
  • Silencing PAPP-A enhanced RCT capacity and increased the expression of key RCT-related genes (LXRα, ABCA1, ABCG1, SR-B1).
  • PAPP-A inhibition repressed the PI3K/Akt pathway and reduced pro-inflammatory cytokine secretion via the NF-κB pathway.

Conclusions:

  • PAPP-A promotes atherosclerosis in apoE-/- mice by hindering RCT and promoting inflammation.
  • Targeting PAPP-A represents a potential therapeutic approach for mitigating atherosclerosis progression.
Abstract

Keywords:
AtherosclerosisInflammationPregnancy-associated plasma protein-AReverse cholesterol transport

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