Discrimination of dyslipidemia types with ATR-FTIR spectroscopy and chemometrics associated with multivariate analysis of the lipid profile, anthropometric, and pro-inflammatory biomarkers.

BACKGROUND: Obesity, dyslipidemia, and low-grade inflammatory state form a triad of self-sustaining metabolic dysfunction. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy is a simple, rapid, and non-destructive technique that generates spectral fingerprints of biomolecules that can be correlated with metabolic changes. We verified the efficiency of ATR-FTIR spectroscopy in blood plasma (n = 74) to discriminate the types of dyslipidemias and suggest metabolic inflammatory changes. METHODS: Principal Component Analysis (PCA) was performed on the biochemical and anthropometric data to verify whether the dyslipidemia types share a similar biochemical profile plausible of discrimination in chemometric modeling. To discriminate the types of dyslipidemias based on spectral data, Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) was used and validated with leave-one-out cross-validation. RESULTS: Although no significant difference was obtained between the types of dyslipidemia and normal subjects by CRP, leptin, and cfDNA, there was a significant difference between normal subjects vs combined hyperlipidemia (CH) + hypercholesterolemia (HCL) + hypertriglyceridemia (HTG) (p < 0.05) by the 1245 cm-1 peak [νas(PO2-)] (possible indication of chronic inflammation by increased cfDNA). The area under the curve of the region between 1770 and 1720 cm-1 was significantly increased for CH in relation to other dyslipidemias and normal subjects. Furthermore, there were significant differences for the main representative peaks of lipids, proteins, carbohydrates, and nucleic acids between the types of dyslipidemias and between the types of dyslipidemias and normal subjects. The OPLS-DA model achieved 100 % accuracy with 1 latent variable and Standard Error of Cross-Validation (SECV) < 0.004 for all types of dyslipidemia  and the control group. CONCLUSIONS: Our results suggest that ATR-FTIR spectroscopy associated with chemometric modeling is a plausible applicant for screening the types of dyslipidemias. However, more extensive studies should be conducted to verify the real applicability in clinical analysis laboratories or medical clinics.

Detection of metabolic syndrome with ATR-FTIR spectroscopy and chemometrics in blood plasma.

Metabolic Syndrome (MetS) is a constellation of 3 or more risk factor (abdominal obesity, high triglycerides, low HDL-c, high blood pressure, and elevated blood glucose) for atherosclerotic cardiovascular disease. Considering these systemic metabolic changes in the biochemical pathways of all biomolecules, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy is a rapid, low-cost, and reagent-free alternative technique capable of identifying spectral biomarkers that differentiate subjects with MetS from control. In this study, plasma samples from 74 subjects (14 MetS, 60 control) were analyzed on the ATR-FTIR spectrophotometer. The objective was to differentiate subjects with MetS from control with supervised chemometrics modeling (Orthogonal Partial Least Squares-Discriminant Analysis, OPLS-DA). Additionally, the inflammatory status of subjects with MetS and control (supervised by C-reactive protein - CRP, leptin, and cell-free DNA - cfDNA) was verified. The OPLS-DA model achieved 100% sensitivity and specificity in cross-validation. For 1 latent variable (93.4% of variance), RMSECV < 0.002, PRESS CV < 0.0001, and R2 > 0.9999 was obtained. Significant spectrochemical differences (p < 0.05) were found between MetS and control subjects in the following biomolecular regions (cm-1): 1717-1703 [ν(CO) and δ(NH)], 1166-1137 [ν(C-OH) + ν(CO) and ν(CC) + Î´(OH) + ν(CO)], 1113-1040 [ν(PO2-) and ν(C-OH)], and 1027-1008 [ν(CO) and v(CH2OH)]. In the OPLS-DA model loadings, amide I [1720-1600 cm-1, ν(CO)] and amide II [1570-1480 cm-1, δ(NH) + ν(CH)] had significantly greater weight than all other regions. There was a significant difference in inflammatory status between MetS patient and control (p < 0.05 for CRP and leptin, and p < 0.01 for cfDNA).

Vascular endothelial growth factor association with angiopoietin 1 promotes improvement in ventricular function after ischemic cardiomyopathy induced in mini pigs.

PURPOSE: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. METHODS: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. RESULTS: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. CONCLUSION: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.

Vascular endothelial growth factor association with angiopoietin 1 promotes improvement in ventricular function after ischemic cardiomyopathy induced in mini pigs

Abstract Purpose: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. Methods: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. Results: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. Conclusion: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.

Cell Therapy in Ischemic Heart Disease: Interventions That Modulate Cardiac Regeneration.

The incidence of severe ischemic heart disease caused by coronary obstruction has progressively increased. Alternative forms of treatment have been studied in an attempt to regenerate myocardial tissue, induce angiogenesis, and improve clinical conditions. In this context, cell therapy has emerged as a promising alternative using cells with regenerative potential, focusing on the release of paracrine and autocrine factors that contribute to cell survival, angiogenesis, and tissue remodeling. Evidence of the safety, feasibility, and potential effectiveness of cell therapy has emerged from several clinical trials using different lineages of adult stem cells. The clinical benefit, however, is not yet well established. In this review, we discuss the therapeutic potential of cell therapy in terms of regenerative and angiogenic capacity after myocardial ischemia. In addition, we addressed nonpharmacological interventions that may influence this therapeutic practice, such as diet and physical training. This review brings together current data on pharmacological and nonpharmacological approaches to improve cell homing and cardiac repair.