Related Experiment Video

Updated: Oct 15, 2026

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Thrombospondin-1 induces endothelial cell apoptosis and inhibits angiogenesis by activating the caspase death pathway

J E Nör1, R S Mitra, M M Sutorik

  • 1Department of Oral Medicine/Pathology/Oncology, University of Michigan School of Dentistry, Ann Arbor, MI, USA.

Journal of Vascular Research
|June 22, 2000
PubMed

Insights

Thrombospondin-1 (TSP1) inhibits new blood vessel formation by inducing endothelial cell apoptosis. This occurs via increased Bax, decreased Bcl-2, and caspase-3 activation, a process blocked by caspase-3 inhibitors.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Thrombospondin-1 (TSP1) is a known inhibitor of angiogenesis.
  • The precise molecular mechanisms linking TSP1's induction of endothelial cell apoptosis and its anti-angiogenic effects remain unclear.

Purpose of the Study:

  • To elucidate the molecular pathways through which TSP1 inhibits angiogenesis.
  • To investigate the role of apoptosis-related proteins and caspases in TSP1-mediated anti-angiogenic effects.

Main Methods:

  • Assessed changes in Bax and Bcl-2 expression in endothelial cells treated with TSP1.
  • Investigated caspase-3 activation and processing in response to TSP1.
  • Utilized caspase-3 inhibitor z-DEVD-FMK to block TSP1 effects in vitro and in vivo.
  • Examined TSP1's impact on VEGF-mediated Bcl-2 expression.
  • Evaluated TSP1's effect on neovascularization in SCID mouse sponge implants.

Main Results:

  • TSP1 treatment increased Bax expression and decreased Bcl-2 expression in endothelial cells.
  • TSP1 induced the processing of caspase-3 into proapoptotic forms.
  • The caspase-3 inhibitor z-DEVD-FMK abrogated TSP1-induced endothelial cell apoptosis and angiogenesis inhibition.
  • TSP1 attenuated VEGF-induced Bcl-2 expression and inhibited angiogenesis in vivo.
  • TSP1 suppressed neovascularization in SCID mouse sponge implants.

Conclusions:

  • TSP1 induces endothelial cell apoptosis and inhibits neovascularization by modulating the expression of survival genes (Bax, Bcl-2).
  • Activation of caspase-3 is a critical mediator of TSP1's anti-angiogenic and pro-apoptotic functions.
  • These findings clarify the molecular basis of TSP1's role in regulating blood vessel formation.

More Related Videos

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...