Plasma protein thiolation index (PTI) as a potential biomarker for left ventricular hypertrophy in humans

Abstract

Background Left ventricular hypertrophy (LVH) has been associated with oxidative stress, although not with the protein thiolation index (PTI). This study explored the potential use of PTI as a biomarker of oxidative stress in patients with LVH. Methods We recruited 70 consecutive patients (n = 35 LVH and n = 35 non-LVH) based on an echocardiography study in our institution (left ventricular mass indexed to body surface area). Plasma levels of both S-thiolated protein and total thiols were measured as biomarkers of oxidative stress by spectrophotometry, and PTI was calculated as the molar ratio between S-thiolated proteins and the total thiol concentration. Results Values for plasma S-thiolated proteins were higher in patients with LVH than in the control group (P = 0.01). There were no differences in total thiols between the LVH group and the control group. Finally, PTI was higher in patients with LVH than in the control group (P = 0.001). The area under the ROC curve was 0.75 (95% CI, 0.63–0.86; P<0.001), sensitivity was 70.6%, and specificity was 68.6%, thus suggesting that PTI could be used to screen for LVH. A multivariable logistic regression model showed a positive association (P = 0.02) between PTI and LVH (OR = 1.24 [95% CI, 1.03–1.49]) independently of gender (OR = 3.39 [95% CI, 0.60–18.91]), age (OR = 1.03 [95% CI, 0.96–1.10]), smoking (OR = 5.15 [95% CI, 0.51–51.44]), glucose (OR = 0.99 [95% CI, 0.97–1.01]), systolic arterial pressure (OR = 1.10 [CI 1.03–1.17]), diastolic arterial pressure (OR = 0.94 [CI 0.87–1.02]), dyslipidemia (OR = 1.46 [95% CI, 0.25–8.55]), estimated glomerular filtration rate (OR = 0.98 [95% CI, 0.96–1.01]), body mass index (OR = 1.03 [95% CI, 0.90–1.10]), and valvular and/or coronary disease (OR = 5.27 [95% CI, 1.02–27.21]). Conclusions The present study suggests that PTI could be a new biomarker of oxidative stress in patients with LVH.

Inhibition of the NFATc4/ERK/AKT Pathway and Improvement of Thiol-Specific Oxidative Stress by Dronedarone Possibly Secondary to the Reduction of Blood Pressure in an Animal Model of Ventricular Hypertrophy

“…Recently, our group has shown that PTI could be a new biomarker of oxidative stress in patients with LVH: PTI was higher in patients with LVH compared with patients without LVH, the area under the receiver operating characteristic curve was 0.75, sensitivity was 70.6%, and specificity was 68.6%. Thus, PTI could be used to screen for LVH (Quintana-Villamandos et al, 2019). In the present study, we have observed the same result, the SHR control group showed a markedly higher PTI than the WKY control group.…”

“…On the other hand, an enhanced oxidative stress status may be related to the induction or maintenance of cardiac remodeling by its action on these signaling pathways ( Maulik and Kumar, 2012 ; Sag et al, 2014 ; Moris et al, 2017 ). Recently, our group has demonstrated that patients with LVH show increased levels of protein thiolation index (PTI; Quintana-Villamandos et al, 2019 ).…”

OXY-SCORE: a new perspective for left ventricular hypertrophy diagnosis

“…Recently, our group investigated PTI, a biomarker of oxidative stress that combines oxidative damage (S-thiolated proteins) and antioxidant capacity (thiols) in plasma from patients with LVH. 16 PTI showed an AUC of 0.75, with sensitivity of 70.6% and specificity of 68.8%, thus suggesting that it could be used to screen for LVH. 16 The OXY-SCORE (combining several biomarkers of oxidative damage and antioxidant capacity) shows similar AUC values (0.74) and diagnostic validity indexes; however, it exhibits a limited variability, and precision and completeness are expected to increase with the number of parameters included.…”

“…11 In addition, the global index of plasma oxidative stress was shown to be a therapeutic target in coronary artery remodeling in a model animal with primary hypertension. 13 Therefore, the global index Reproduced with permission from Quintana-Villamandos et al 16 The data are expressed as the mean ± SEM, frequency (percentage). * p < 0.001.…”

“…Recently, we have described a new biomarker for LVH in humans. 16 The plasma protein thiolation index (PTI) is a biomarker of oxidative stress that is defined as the molar ratio of S-thiolated proteins (oxidative damage) to free protein thiols (antioxidant capacity) in plasma. 17 However, the OXY-SCORE exhibits limited variability, and the precision and completeness are expected to increase with the number of parameters included.…”