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Updated: Jul 2, 2026

An Intact Pericardium Ischemic Rodent Model
Published on: September 2, 2021
Perlecan is critical for heart stability
Philipp Sasse1, Daniela Malan, Michaela Fleischmann
1Institute of Physiology I, Life & Brain Center, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Insights
Perlecan is crucial for early heart development, preventing embryonic lethality by maintaining cardiac structural integrity. Loss of perlecan leads to mechanical instability in embryonic hearts and impaired function in adult hearts after injury.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Extracellular Matrix Research
Background:
- Perlecan, a heparan sulfate proteoglycan, is vital in basement membranes and mesenchymal tissues.
- Perlecan gene mutations in mice cause embryonic lethality, primarily due to cardiac abnormalities.
- Understanding perlecan's role in cardiac development and function is essential.
Purpose of the Study:
- Investigate the mechanism behind perlecan-related embryonic lethality.
- Determine the pathophysiological relevance of perlecan for heart function.
Main Methods:
- Utilized perlecan-deficient murine embryonic stem cells.
- Analyzed mechanical stability of developing hearts via dextran microinjection.
- Examined basement membrane and cell-cell junction formation using electron microscopy, immunohistochemistry, and western blotting.
Main Results:
- Perlecan deficiency did not affect sarcomere formation or cardiomyocyte electrophysiology.
- Early embryonic hearts (before E10.5) showed mechanical instability.
- Perlecan-null hearts had reduced collagen IV and laminin levels and lacked basement membranes.
- Infarcted hearts from heterozygous mice exhibited impaired function compared to wild-type.
Conclusions:
- Perlecan is critical for maintaining cardiac integrity during embryonic development.
- Perlecan is important for adult heart function following injury.
Aims:
Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, and tissue repair. Loss-of-function mutations in the perlecan gene in mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of the present study was to investigate the mechanism underlying the early embryonic lethality and the pathophysiological relevance of perlecan for heart function.
Methods And Results:
Perlecan-deficient murine embryonic stem cells were used to investigate the myofibrillar network and the electrophysiological properties of single cardiomyocytes. The mechanical stability of the developing perlecan-deficient mouse hearts was analysed by microinjecting fluorescent-labelled dextran. Maturation and formation of basement membranes and cell-cell contacts were investigated by electron microscopy, immunohistochemistry, and western blotting. Sarcomere formation and cellular functional properties were unaffected in perlecan-deficient cardiomyocytes. However, the intraventricular dye injection experiments revealed mechanical instability of the early embryonic mouse heart muscle wall before embryonic day 10.5 (E10.5). Accordingly, perlecan-null embryonic hearts contained lower amounts of the critical basement membrane components, collagen IV and laminins. Furthermore, basement membranes were absent in perlecan-null cardiomoycytes whereas adherens junctions formed and matured around E9.5. Infarcted hearts from perlecan heterozygous mice displayed reduced heart function when compared with wild-type hearts.
Conclusion:
We propose that perlecan plays an important role in maintaining the integrity during cardiac development and is important for heart function in the adult heart after injury.
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