Castaldo, Luigi (2020) Polyphenols in red wine and common genetic variants influencing cardiovascular diseases. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Polyphenols in red wine and common genetic variants influencing cardiovascular diseases
Date: 10 January 2020
Number of Pages: 102
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Clinica e Chirurgia
Dottorato: Terapie avanzate medico-chirurgiche
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
Di Minno,
Di Minno, GiovanniUNSPECIFIED
Ritieni, AlbertoUNSPECIFIED
Date: 10 January 2020
Number of Pages: 102
Keywords: Red wine, polyphenols, Orbitrap, carotid intima-media thickness
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/10 - Chimica degli alimenti
Area 06 - Scienze mediche > MED/09 - Medicina interna
Date Deposited: 22 Mar 2020 10:31
Last Modified: 10 Nov 2021 11:33

Collection description

ABSTRACT Diet is a pivotal constituent of a healthy lifestyle. Mediterranean diet is the typical dietary pattern consumed around the Mediterranean Basin, that drew the attention of medical professionals by proving protection against chronic disease morbidity and contribute to a favorable health status. In the Mediterranean basin, the most widely consumed alcoholic beverage is wine, while coffee is the main non-alcoholic beverage. Wine is a popular alcoholic beverage that has been consumed for hundreds of years. Benefits from moderate alcohol consumption have been widely supported by the scientific literature and, in this line, red wine intake has been related to a lesser risk for coronary heart disease (CHD). Experimental studies and meta-analyses have mainly attributed this outcome to the presence in red wine of a great variety of polyphenolic compounds such as resveratrol, catechin, epicatechin, quercetin, and anthocyanin. Resveratrol is considered the most effective wine compound with respect to the prevention of CHD because of its antioxidant properties. The mechanisms responsible for its putative cardioprotective effects would include changes in lipid profiles, reduction of insulin resistance, and decrease in oxidative stress of low-density lipoprotein cholesterol (LDL-C). In this sense, the first part of my Ph.D. project summarizes the accumulated evidence correlating moderate red wine consumption with prevention of CHD by focusing on the different mechanisms underlying this relationship. Furthermore, in this thesis work was developed a method for simultaneous investigation of polyphenol compounds in red wine samples using ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). In addition, total phenols content, as well as antioxidant activity in red wine samples, were also investigated. Moreover, to expand the understanding of this current topic and evaluate the potential health benefits of moderate red wine consumption, a monocentric, open-label, non-randomized, parallel-group clinical trial was designed. Healthy volunteers will be clinically evaluated by medical staff working at the Prevention Unit of the Atherosclerosis of the Cardiology Center Monzino (Milan, Italy), in order to evaluate the cardioprotective effect of wine (red and white) and nutraceutical formulation of resveratrol, the main active compound found in wine. Nevertheless, there were several problems approving the protocol by the Ethics Committee on the Monzino Cardiology Center. This led to a delay in the study. Currently, the protocol is being redesigned for next evaluation by Ethics Committee. In addition, in my Ph.D. I have also investigated the qualitative and quantitative profile of the bioactive compounds of coffee by-product using UHPLC-High resolution mass spectrometry. Moreover, I studied the antioxidant and antifungal activity of this innovative source in order to use this by-product as an innovative source of high added-value ingredients. On the other hand, I have investigated the possible associations between common genetic variants and surrogate markers of coronary artery disease. Therefore, in this part of my Ph.D. I investigated three single nucleotide polymorphisms (SNPs) in PNPLA3 (rs738409), TM6SF2 (rs10401969) and GCKR (rs1260326). These SNPs have been associated with non-alcoholic fatty liver disease (NAFLD). NAFLD and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. The aim of this part was to investigate whether NAFLD-associated SNPs were also associated with markers of subclinical atherosclerosis, specifically carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in a European population, the IMPROVE study. IMPROVE study participants (n=3711) were free from clinically overt CVD but had at least three CVD risk factors. Linear regression with an additive genetic model, adjusted for age, sex and population stratification, were used to test for association of SNPs with c-IMT, ICCAD, alanine aminotransferase (ALT) and metabolic traits (body mass index BMI, glucose and lipids levels). In secondary analyses, the association of the SNPs with c-IMT and ICCAD was tested after stratification by ALT levels. No associations were observed between rs738409, rs1260326, rs10401969 and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p < 0.001). Moreover, rs738409-G was associated with higher BMI (p = 0.045). Rs1260326-T was associated with lower TG level (p < 0.001) and with lower BMI (p = 0.028). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and p = 0.021, respectively). In this population at high cardiovascular risk, NAFLD-associated genetic variants did not demonstrate significant effects on measures of sub-clinical atherosclerosis, except in the presence of high circulating ALT. These results support possible mediating function of impaired liver function on atherosclerosis.


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