Noninvasive assessment of endothelial function in the skin microcirculation

BACKGROUND: The structure and function of blood vessels varies along the vascular tree. Endothelial dysfunction is a hallmark of increased cardiovascular (CV) risk that can be assessed by several methods, some of which are invasive and of restricted application. The aim of this study was to determine whether the laser Doppler response of skin microcirculation to acetylcholine, reflects that of conduit artery assessed by brachial artery flow-mediated dilation (FMD). METHODS: Noninvasive measurement of endothelium-dependent vasodilation in the skin microcirculation by laser Doppler flowmetry (LDF) in response to a local transdermal iontophoretic application of acetylcholine (Ach-SkBF) is an operator-independent method. Ach-SkBF and FMD were measured in the nondominant upper limb of 55 unselected consecutive patients admitted in our department for evaluation of CV risk factors. RESULTS: Ach-SkBF was (mean +/- s.d. (min-max)) 490 +/- 414%, (10-1667%) and FMD was 3.77 +/- 3.01% (0.91-10.91). A strong linear relationship was found between Ach-SkBF and FMD: Ach-SkBF = 122.7 FMD + 25.8 (r = 0.92, P < 0.0001). CONCLUSIONS: Endothelial dilatory response to increased blood flow and to acetylcholine are similar in large arteries and in the skin microvasculature. Thus, measurement of blood flow changes in the skin microcirculation using LDF coupled with acetylcholine iontophoresis represents a technically challenging and reliable noninvasive method for the assessment of endothelial function within a large range of normal and altered endothelium responses

Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease

The pathophysiology of sporadic Alzheimer\u27s disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD