Selective microvascular dysfunction in mice lacking the gene encoding for desmin

The intermediate filament desmin has a key role in the integrity and contra ctility of skeletal and cardiac myocytes. Its absence or aggregation leads to cardiomyopathies. In arteries desmin is distributed heterogeneously; vas cular 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 mou nted in vitro in arteriographs. Desmin was located exclusively in smooth mu scle cells. In arteries from des-/- mice, pressure-induced (myogenic) tone was unchanged, but agonist-induced tone decreased in resistance arteries (n o change in large arteries). Flow (shear stress)- and acetylcholine-induced , endothelium-dependent dilation, as well as endothelium-independent dilati on, were also decreased in resistance arteries. To our knowledge, this is the first study of vascular contractile and dilat ory functions in arteries lacking desmin. Although vascular reactivity was normal in large arteries, it decreased strongly in small resistance arterie s. Thus, desmin is required in vascular smooth muscle cells and in resistan ce 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 dise ases.