Selective microvascular dysfunction in mice lacking the gene encoding for desmin.
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.
Loufrani
Laurent
L
Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, IFR-Circulation-Paris-Nord, Paris VII University, Paris, France.
Matrougui
Khalid
K
Li
Zhenlin
Z
Levy
Bernard I
BI
Lacolley
Patrick
P
Paulin
Denise
D
Henrion
Daniel
D
D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000502:physiology; D001158:Arteries / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000209:etiology; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000502:physiology; D046508:Culture Techniques; D003893:Desmin / Q000235:genetics* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000033:anatomy & histology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000502:physiology; D008954:Models, Biological; D009119:Muscle Contraction; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D003893:Desmin; D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester