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

Area of Science:

• Cardiovascular Physiology
• Atherosclerosis Pathogenesis
• Microvascular Function

Background:

• Human cutaneous circulation serves as a model for microvascular dysfunction, an early aspect of atherosclerosis.
• Elevated low-density lipoproteins (LDL) are atherogenic and linked to coronary atherosclerosis severity via lectin-like oxidized LDL receptors (LOX-1).

Purpose of the Study:

• To investigate the correlation between cutaneous microvascular dysfunction and serum markers of LDL cholesterol.
• To assess if endothelial nitric oxide- (NO-) dependent vasodilation is impaired in relation to LDL, oxidized LDL, and soluble LOX-1 (sLOX-1) levels.

Main Methods:

• 53 healthy adults (aged 52±8 years) with varying LDL levels (72-233 mg/dL) participated.
• Skin blood flow was measured using laser Doppler flowmetry during local heating (42°C).
• Nitric oxide-dependent vasodilation was quantified by blocking NO synthase with L-NAME and normalizing to maximal cutaneous vascular conductance (CVC).

Main Results:

• NO-dependent vasodilation significantly decreased as a linear function of serum LDL concentration (R(2)=0.303, p<0.001).
• Impaired vasodilation was also correlated with higher levels of oxidized LDL (R(2)=0.214, p<0.001) and soluble LOX-1 (R(2)=0.259, p=0.026).
• No significant relationship was found between vasodilation and high-density lipoprotein (HDL) concentration (R(2)=0.003, p=0.68).

Conclusions:

• Hypercholesterolemia-induced microvascular dysfunction is associated with elevated LDL and oxidized LDL markers.
• This dysfunction involves a progressive reduction in NO-dependent vasodilation, which is measurable in the skin microcirculation.