Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor concentrations

The human cutaneous circulation is an accessible and representative regional circulation for investigating mechanisms of microvascular dysfunction, a systemic disease process occurring early in the pathogenesis of atherosclerosis. Elevated concentrations of low-density lipoproteins ([LDL]) are highly atherogenic and independently associated with the severity of coronary atherosclerosis through their actions on the lectin-like oxidized LDL receptors (LOX-1). We hypothesized that cutaneous microvascular dysfunction, as measured by a decrement in endothelial nitric oxide- (NO-) dependent vasodilation during local heating, would be correlated with serum [LDL], oxidized [LDL], and soluble LOX-1 receptors [sLOX-1]. Intradermal microdialysis fibers were placed in the skin of 53 otherwise healthy men and women (aged 52 ± 8 years) whose serum [LDL] ranged from 72 to 233 mg/dL. Skin blood flow was measured by laser Doppler flowmetry over a local forearm skin site as it was heated (42 °C) to induce sustained local vasodilation. After flux plateaued, L-NAME was infused to block endothelial NO synthase in order to determine the NO-dependent portion of the vasodilatory response. Data were normalized to maximal cutaneous vascular conductance (CVC). NO-dependent vasodilation was reduced as a linear function of [LDL] (R2 = 0.303, p < 0.001), oxidized [LDL] (R2 = 0.214, p < 0.001), and [sLOX-1] (R2 = 0.259, p = 0.026) but was unrelated to high-density lipoprotein (HDL) concentration (R2 = 0.003, p = 0.68). Hypercholesterolemia-induced microvascular dysfunction is related to various LDL markers and involves a reduction in NO-dependent vasodilation that appears to be a progressive process measurable in the skin microcirculation.

► Atherosclerotic microvascular dysfunction (MVD) is a systemic disease process.
► Human skin is an accessible regional circulation to investigate MVD.
► NO-dependent vasodilation is reduced as a linear function of LDL, oxLDL and sLOX-1.
► MVD is a progressive process measurable in the skin microcirculation.