Abstract

Objectives. To evaluate the plasma aminothiol profile (PAP) and serum gamma-glutamyltransferase (GGT) activity, as well as plasma folate, vitamin B12, and vitamin B6 concentrations, in 326 apparently healthy subjects from the Azores archipelago (Portugal). Also eventual relationships of PAP with conventional risk factors for atherosclerosis were investigated, aiming at the finding of early blood markers of the disease. Design and Methods. This was an observational cross-sectional study, where participants were split into two groups: one with a normal and another with an altered PAP (at least one aminothiol out of its reference concentration range). Results. About 76% of subjects had an altered PAP, mainly due to low glutathione levels (<1.5 μmol/L), mostly associated with normal GGT activity. Prevalence of hyperhomocysteinemia was 10%, where only 33% had some B-vitamin deficiency. The risk for atherosclerosis was more evidenced in subjects exhibiting both deficient GSH concentration and increased serum GGT activity. Conclusions. An altered PAP, namely, when caused by low GSH levels in the absence of alterations in the Hcy, or Cys, or Cys-Gly concentrations and in serum GGT activity, might reveal a subclinical stage of atherogenesis and should be explored as a potential early marker of atherosclerosis.

Highlights

  • Atherosclerosis (AT), the major origin of cardiovascular disease (CVD), is a chronic multifactorial condition which can develop as a silent and progressive disease [1], whose clinical symptoms arise in advanced stages of the pathology as irreversible or deadly

  • Serum GGT activity is conventionally interpreted as a marker of alcohol abuse and liver dysfunction, and it has been shown to correlate with CVD [10]

  • In altered PAP (aPAP) subjects where GSH was the only thiol at altered concentration, we further examined the aPAP-1 individuals, according to their GGT activity (Table 4)

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Summary

Introduction

Atherosclerosis (AT), the major origin of cardiovascular disease (CVD), is a chronic multifactorial condition which can develop as a silent and progressive disease [1], whose clinical symptoms arise in advanced stages of the pathology as irreversible or deadly. The major plasma aminothiols are homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), and glutathione (GSH), which serve numerous vital functions, including detoxification and regulation of cellular metabolism, enzymatic activity, protein synthesis and structure [4], protection of cellular components against oxidative stress [5], formation of bioactive molecules, and participation in amino acid transport, among others [6]. All these aminothiols interact via redox, namely, disulfide exchange reactions, and reduced, oxidized, and protein bound forms of these species comprise a dynamic system referred to as the redox thiol status [7].

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