Vascular involvement in the pathogenesis of idiopathic inflammatory myopathies

The identification of the exact role of the involvement of the vascular system in the pathogenesis of idiopathic inflammatory myopathies (IIMs) has been the task of several scientific investigations during the recent years. The observations that microcirculatory disturbances might play a major-if not perhaps the primary-role in IIMs have gained wide recognition among the scientific community and led to different experimental and clinical attempts to study the role of microvessels in IIMs. During the past years, the 'Vascular Hypothesis' of the pathogenesis of IIMs has been co-developed in our laboratory supported by experimental and clinical data. This hypothesis is based on assumptions that phenotypically altered microvessels might affect the local circulation of the muscle and hence lead to the development of tissue hypoxia and metabolic alterations. Subsequently, local hypoxia in muscle tissue could lead to muscle weakness and muscle fatigue, which are the most prominent clinical signs in IIM patients. This hypothesis is further supported by the reported benefits of physical exercise and associated molecular alterations in muscle in patients with IIMs. This review will highlight some of the most important findings that elucidate the role of vascular endothelial cell dysfunction and hypoxia in the pathogenesis of IIMs.