Related Experiment Videos

ADAMDEC-1 promotes atherosclerosis progression by interacting with ACTN4 and modulating the PTEN-PI3K/AKT signaling

Yanmei Zhang1, Chengwei Dai2, Lianxin Luo2

  • 1Department of Cardiology, The Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road, Economic Development Zone, Hefei, 230601, Anhui, China.

Molecular and Cellular Biochemistry
|August 20, 2026
PubMed

Insights

ADAMDEC-1 contributes to atherosclerosis (AS) by interacting with ACTN4 and influencing vascular smooth muscle cell function. Targeting ADAMDEC-1 may offer new therapeutic strategies for cardiovascular disease.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Immunology

Background:

  • Atherosclerosis (AS) is a major cause of cardiovascular disease with unmet therapeutic needs.
  • ADAMDEC-1 (ADAM-like decysin-1) is primarily known for immune regulation, with its role in vascular injury undefined.
  • Understanding novel molecular mechanisms in AS is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the role of ADAMDEC-1 in experimental atherosclerosis.
  • To elucidate the signaling pathways and protein interactions involved in ADAMDEC-1's function in AS.
  • To determine if ADAMDEC-1 contributes to vascular smooth muscle cell dysfunction.

Main Methods:

  • ADAMDEC-1 was suppressed in a mouse model of AS using AAV-mediated shRNA.
  • Human vascular smooth muscle cells (HVSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic atherosclerotic stress.
  • Techniques included Western blotting, IP-MS, Co-IP, immunofluorescence, CCK-8, Transwell, scratch wound-healing, and flow cytometry.

Main Results:

  • ADAMDEC-1 knockdown reduced aortic lesion burden and improved lipid profiles in AS mice.
  • ADAMDEC-1 was found to interact with ACTN4, and this interaction was increased by ox-LDL.
  • ADAMDEC-1 knockdown restored PTEN expression and attenuated PI3K/AKT signaling, while ACTN4 knockdown impaired ox-LDL-induced HVSMC proliferation and migration.

Conclusions:

  • ADAMDEC-1 plays a significant role in experimental atherosclerosis.
  • The study identifies a novel pathway involving ADAMDEC-1, ACTN4, and PTEN/PI3K/AKT signaling in AS.
  • ACTN4 is essential for the pro-atherosclerotic effects of ox-LDL on HVSMCs, highlighting potential therapeutic targets.

Keywords:
ACTN4ADAMDEC-1AtherosclerosisPTEN/PI3K/AKTVascular smooth muscle cell

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...