Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.

• Keywords
• 4-methylcathechol, familial hypercholesterolemia, lipid apheresis, platelet,
• MeSH
• Hyperlipoproteinemia Type II * drug therapy   MeSH
• Cholesterol, LDL MeSH
• Humans MeSH
• Antibodies, Monoclonal pharmacology   therapeutic use   MeSH
• Proprotein Convertase 9 MeSH
• Proprotein Convertases therapeutic use   MeSH
• Blood Component Removal * methods   MeSH
• Subtilisin MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 4-methylcatechol MeSH Browser
• Cholesterol, LDL MeSH
• Antibodies, Monoclonal MeSH
• Proprotein Convertase 9 MeSH
• Proprotein Convertases MeSH
• Subtilisin MeSH

Interest in understanding the mechanisms of the positive effects of dietary phenolic and polyphenolic compounds on human health has markedly increased in recent years [...].

• MeSH
• Diet * MeSH
• Phenols * pharmacology   MeSH
• Humans MeSH
• Polyphenols MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH
• Names of Substances
• Phenols * MeSH
• Polyphenols MeSH

Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.

• Keywords
• 3-hydroxyphenylacetic acid, artery, blood pressure, coronary, flavonoids, gut microbiota, metabolite, pig, rat, vasorelaxation,
• MeSH
• Phenylacetates pharmacology   MeSH
• Flavonoids metabolism   pharmacology   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Rats, Inbred SHR MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 3-hydroxybenzeneacetic acid MeSH Browser
• Phenylacetates MeSH
• Flavonoids MeSH