Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease

Abstract

Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66±7 years) and 46 healthy men (aged 66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme-linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, α-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.

Metabolomic profile of arterial stiffness in aged adults

“…29 Disturbances in fuel oxidation pathways have been previously linked to arterial disease. Zagura et al 11 used PWV to study male subjects with symptomatic peripheral arterial disease. They found a signature comprising lactate, carnitine and amino acids that were associated with PWV in their cohort.…”

“…8 Certain traditional risk factors beyond ageing have been associated with arterial stiffness including insulin resistance/metabolic syndrome. 9,10 Several studies have reported alterations in fuel-metabolismrelated markers both in patients with clinically significant arterial stiffness [10][11][12] and in subjects with subclinical changes in arterial stiffness. 9,[13][14][15] One interpretation is that arterial stiffening may drive metabolic changes through impairments in distal tissue perfusion.…”

Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease

“…A higher AIX and aPWV has been shown to be correlated with 8-iso-prostaglandin F2a (F2-IsoPs), an indicator of oxidative stress, only in PAD patients and not in controls [ 44 ]. Likewise, in a metabolic profiling of PAD patients, oxidized LDL was independently associated with the aPWV, suggesting that arterial stiffening may be determined by the level of oxidative modifications [ 45 ]. Furthermore, arterial elasticity is a measure of vascular compliance and distensibility in addition to arterial stiffness; it can be quantified based on a modified Windkessel model, with C1 being a marker for large artery elasticity and C2 a marker for small artery elasticity [ 46 ].…”

Targeted metabolomic approach in men with carotid plaque

“…This could be an innovative way to investigate the molecular basis of vascular disease. In this regard, recent metabolic phenotyping and profiling studies have obtained promising results on the atherosclerotic plaque of both carotid and coronary arteries and peripheral artery diseases [ 5 – 7 ].…”