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

W. Larry Kenney, Joseph Gerard Cannon, Lacy M. Alexander

Research output: Contribution to journalArticle

13 Citations (Scopus)

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±8years) whose serum [LDL] ranged from 72 to 233mg/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.

Original languageEnglish (US)
Pages (from-to)112-117
Number of pages6
JournalMicrovascular Research
Volume85
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

LDL Lipoproteins
Skin
Nitric Oxide
Vasodilation
Serum
Microcirculation
Lipoproteins
LDL Receptors
NG-Nitroarginine Methyl Ester
HDL Lipoproteins
Lectins
Nitric Oxide Synthase
Class E Scavenger Receptors
Blood
Laser-Doppler Flowmetry
Fluxes
Heating
Microdialysis
Hypercholesterolemia
Fibers

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor concentrations. / Kenney, W. Larry; Cannon, Joseph Gerard; Alexander, Lacy M.

In: Microvascular Research, Vol. 85, No. 1, 01.01.2013, p. 112-117.

Research output: Contribution to journalArticle

Kenney, W. Larry ; Cannon, Joseph Gerard ; Alexander, Lacy M. / Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor concentrations. In: Microvascular Research. 2013 ; Vol. 85, No. 1. pp. 112-117.
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