The influence of the skin site, recording conditions, and the way of expressing data are also reviewed. Finally, we focus on promising tools such as laser speckle contrast imaging. Since the development of methods allowing the study of microcirculation, microvascular dysfunction has been associated with several vascular diseases as well as in aging [100]. The role of generalized microvascular dysfunction in the pathophysiology or as a consequence

of these diseases has also been questioned. Indeed, patients with impaired coronary microvascular function also have evidence of impaired peripheral microvascular function, suggesting a generalized disorder Raf inhibitor in the regulation of the microvasculature [120]. Similar findings have been reported of correlated abnormalities between cutaneous and retinal microvasculature in diabetic patients

[20]. As the skin is readily accessible, it provides an appropriate site to assess peripheral microvascular reactivity. Moreover, recent technological advances have provided simple and non-invasive methods to assess skin microvascular function. Therefore, human cutaneous circulation could be used as a surrogate marker of systemic microvascular function in various diseases. However, this raises the issue of how representative the microcirculation in the skin is to the microcirculation in other organs. To date, the skin has BIBW2992 concentration been used as a model of microcirculation to investigate vascular mechanisms in a variety of diseases, including hypertension and other cardiovascular risk factors [5,45,86], diabetes [20,146], or end-stage kidney disease [82]. Skin microcirculation has also been used as a model of microvascular function in experimental shock

[42]. The issue of human cutaneous circulation as a model of generalized microvascular function has been discussed in a recent viewpoint by Holowatz et al. [65]. In other cases, skin microvasculature is specifically affected, e.g., systemic sclerosis [59,143], burns, flaps, or wounds. Altered skin microvascular function could therefore be a surrogate marker in these pathologies. Finally, non-invasive and reliable tests would be useful to evaluate the effect of drugs on the peripheral microvascular system. Reverse Transcriptase inhibitor For more than two decades, methods for the non-invasive exploration of cutaneous microcirculation have been mainly based on optical microscopy and laser Doppler techniques [19], as well as the evaluation of tissue oxygenation. Capillaroscopy is an optical in vivo microscopy technique allowing direct visualization of superficial skin microvessels, which has been mostly used in the study of rheumatic diseases, especially systemic sclerosis [27]. More sophisticated techniques have recently been developed, including OPS imaging [56] and, most recently, SDF imaging [54]. Besides microscopy techniques, laser Doppler provides an index of skin perfusion by measuring the Doppler shift induced by coherent light scattering by moving red blood cells [126].