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Selective microvascular dysfunction in mice lacking the gene encoding for desmin
Laurent Loufrani1, Khalid Matrougui, Zhenlin Li
1Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, IFR-Circulation-Paris-Nord, Paris VII University, Paris, France.
Abstract:
The intermediate filament desmin has a key role in the integrity and contractility of skeletal and cardiac myocytes. Its absence or aggregation leads to cardiomyopathies. In arteries desmin is distributed heterogeneously; vascular disorders might also occur in its absence. We studied endothelial and muscular functions in arteries from mice lacking desmin (des-/-), compared with control (des+/+). Carotid and mesenteric resistance arteries were mounted in vitro in arteriographs. Desmin was located exclusively in smooth muscle cells. In arteries from des-/- mice, pressure-induced (myogenic) tone was unchanged, but agonist-induced tone decreased in resistance arteries (no change in large arteries). Flow (shear stress)- and acetylcholine-induced, endothelium-dependent dilation, as well as endothelium-independent dilation, were also decreased in resistance arteries. To our knowledge, this is the first study of vascular contractile and dilatory functions in arteries lacking desmin. Although vascular reactivity was normal in large arteries, it decreased strongly in small resistance arteries. Thus, desmin is required in vascular smooth muscle cells and in resistance arteries, for efficient control of vascular tone and consequently for an optimal blood flow supply. This microvascular defect found in the absence of desmin might play a major role in myopathies seen in desmin-related diseases.
Insights
Desmin is crucial for vascular smooth muscle cells, particularly in small arteries. Its absence impairs vascular tone and dilation, potentially contributing to desmin-related myopathies.
Area of Science:
- Vascular biology and smooth muscle cell function.
- Intermediate filament protein research.
- Cardiovascular disease mechanisms.
Background:
- Desmin is vital for muscle cell integrity and contractility, with its absence linked to cardiomyopathies.
- Desmin distribution in arteries is heterogeneous, suggesting potential roles in vascular disorders.
- The specific function of desmin in vascular smooth muscle cells and overall vascular health remains largely unexplored.
Purpose of the Study:
- To investigate the role of desmin in vascular endothelial and muscular functions.
- To compare vascular contractile and dilatory responses in arteries from desmin-deficient mice versus controls.
- To elucidate the contribution of desmin to vascular tone regulation and blood flow supply.
Main Methods:
- Utilized arteriography to study carotid and mesenteric resistance arteries from desmin-deficient (des-/-) and control (des+/+) mice.
- Assessed pressure-induced myogenic tone, agonist-induced tone, and flow/acetylcholine-induced dilations.
- Examined desmin localization within arterial tissues, confirming its presence exclusively in smooth muscle cells.
Main Results:
- Desmin was found exclusively in vascular smooth muscle cells.
- While myogenic tone was unaffected, agonist-induced tone was reduced in resistance arteries of des-/- mice.
- Both endothelium-dependent and independent dilations were significantly decreased in resistance arteries lacking desmin.
- Large arteries showed normal vascular reactivity, contrasting with significant deficits in small resistance arteries.
Conclusions:
- Desmin is essential for vascular smooth muscle cells, particularly within resistance arteries.
- The absence of desmin impairs vascular tone control and dilation, impacting optimal blood flow.
- This microvascular dysfunction in desmin deficiency may be a key factor in desmin-related myopathies.