title: Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor concentrations.
abstract: 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] (R(2)=0.303, p<0.001), oxidized [LDL] (R(2)=0.214, p<0.001), and [sLOX-1] (R(2)=0.259, p=0.026) but was unrelated to high-density lipoprotein (HDL) concentration (R(2)=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.
authors.affiliation: Department of Kinesiology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: W Larry
authors.initials: WL
authors.lastname: Kenney
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Cannon
authors.forename: Lacy M
authors.initials: LM
authors.lastname: Alexander
mesh_terms: D000368:Aged; D050197:Atherosclerosis; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D017078:Laser-Doppler Flowmetry / Q000379:methods; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000097:blood*; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D013696:Temperature; D013997:Time Factors; D014664:Vasodilation
chemical_list: D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester