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Updated: Apr 26, 2026
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Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification
Published on: November 20, 2017
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Function and expression differences between ergot and non-ergot dopamine D2 agonists on heart valve interstitial
The Journal of Heart Valve Disease
|August 1, 2014
Summary
Pergolide, a dopamine agonist, increases heart valve cell activity and Dio2 expression via the 5-HT(2B) receptor, unlike pramipexole. These findings suggest a link between pergolide
Area of Science:
- Cardiovascular Pharmacology
- Molecular Biology
- Drug Safety
Background:
- Dopamine D2 agonists, used for Parkinson's disease, include ergot (e.g., pergolide) and non-ergot (e.g., pramipexole) types.
- Pergolide is linked to valvular heart disease due to potent D2 and serotonin 5-HT(2B) receptor agonism.
- Pramipexole has fewer heart valve disease associations, lacking 5-HT(2B) receptor agonism.
Purpose of the Study:
- To investigate the cellular and molecular differences between pergolide and pramipexole in heart valve interstitial cells (VICs).
- To explore the role of the serotonin 5-HT(2B) receptor in mediating drug effects on VICs.
- To identify potential mechanisms linking dopamine agonists to valvular heart disease pathogenesis.
Main Methods:
- Porcine VICs were treated with pergolide or pramipexole.
- [3H]thymidine incorporation assays monitored cellular function.
- Microarray analysis assessed global gene expression changes.
Main Results:
- The serotonin 5-HT(2B) receptor was highly expressed in porcine VICs.
- Pergolide, a 5-HT(2B) agonist, increased [3H]thymidine incorporation and Dio2 expression.
- These pergolide-induced effects were blocked by a 5-HT(2B) antagonist and a PI3K/Akt inhibitor.
- Pramipexole did not induce similar increases in [3H]thymidine incorporation or Dio2 expression.
Conclusions:
- Significant differences exist in the effects of pergolide and pramipexole on VICs, particularly concerning [3H]thymidine incorporation and Dio2 expression.
- The 5-HT(2B) receptor pathway appears to mediate pergolide's pro-proliferative and gene expression effects in VICs.
- These cellular changes may contribute to the pathogenesis of drug-induced valvular heart disease.
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