Acute manifestations of ischemic heart disease are among the most serious and fatal consequences of atherosclerotic processes. In this study, we hypothesized that a soluble proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble bone morphogenetic protein 4 (BMP-4), soluble E-selectin (sE-selectin), soluble endoglin (sENG) and soluble endocan (Endocan) would differ from healthy controls in myocardial infarction (MI) patients admitted to the hospital without any previous history of cardiovascular disease and with no cardioprotective drugs taken before admission. The study was conducted using a cross-sectional design. We analyzed data from 79 patients (mean age 54.1 ± 8.9, 18% of women) admitted for the first manifestation of MI and with no history of cardioprotective treatment use before the event. As a control group, we analyzed 17 age-matched healthy volunteers (mean age 51.5 ± 8.6, 47% of women). In addition to routinely obtaining clinical and laboratory data, we analyzed plasma concentrations of the aforementioned biomarkers using ELISA and Luminex analyses. Patients with MI did not differ from healthy controls in total cholesterol, LDL, non-HDL, and triglyceride levels. PCSK9, BMP-4, and sE-selectin levels did not differ significantly between the MI and the control group. Patients with MI had significantly higher sENG and Endocan levels than the control group. In addition, levels of sENG were significantly higher in patients with higher body mass index (BMI) and in smokers. We demonstrated that sENG could serve as a biomarker reflecting endothelial dysfunction in MI patients without prior treatment for cardiovascular risk factors.

• Keywords
• myocardial infarction, soluble endocan., soluble endoglin,
• MeSH
• Biomarkers blood   MeSH
• Endothelium, Vascular * physiopathology   pathology   metabolism   MeSH
• Adult MeSH
• E-Selectin blood   MeSH
• Endoglin * blood   MeSH
• Myocardial Infarction * blood   pathology   physiopathology   MeSH
• Bone Morphogenetic Protein 4 blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Proteins blood   MeSH
• Proprotein Convertase 9 blood   MeSH
• Proteoglycans blood   MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers MeSH
• BMP4 protein, human MeSH Browser
• E-Selectin MeSH
• Endoglin * MeSH
• ENG protein, human MeSH Browser
• ESM1 protein, human MeSH Browser
• Bone Morphogenetic Protein 4 MeSH
• Neoplasm Proteins MeSH
• PCSK9 protein, human MeSH Browser
• Proprotein Convertase 9 MeSH
• Proteoglycans MeSH
• SELE protein, human MeSH Browser

Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism for this effect is unclear. Carvedilol also prevents the development of various forms of experimental liver injury, but its effect on nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, we determined the effect of carvedilol (10 mg/kg/day p.o.) on bile formation and bile acid (BA) turnover in male C57BL/6 mice consuming either a chow diet or a western-type NASH-inducing diet. BAs were profiled by liquid chromatography-mass spectrometry and BA-related enzymes, transporters, and regulators were evaluated by western blot analysis and qRT-PCR. In chow diet-fed mice, carvedilol increased plasma concentrations of BAs resulting from reduced BA uptake to hepatocytes via Ntcp transporter downregulation. Inhibition of the β-adrenoreceptor-cAMP-Epac1-Ntcp pathway by carvedilol may be the post-transcriptional mechanism underlying this effect. In contrast, carvedilol did not worsen the deterioration of BA homeostasis accompanying NASH; however, it shifted the spectra of BAs toward more hydrophilic and less toxic α-muricholic and hyocholic acids. This positive effect of carvedilol was associated with a significant attenuation of liver steatosis, inflammation, and fibrosis in NASH mice. In conclusion, our results indicate that carvedilol may increase BAs in plasma by modifying their liver transport. In addition, carvedilol provided significant hepatoprotection in a NASH murine model without worsening BA accumulation. These data suggest beneficial effects of carvedilol in patients at high risk for developing NASH.

• Keywords
• bile acids, carvedilol, nonalcoholic steatohepatitis,
• MeSH
• Homeostasis MeSH
• Liver MeSH
• Carvedilol pharmacology   metabolism   MeSH
• Humans MeSH
• Membrane Transport Proteins metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Non-alcoholic Fatty Liver Disease * metabolism   MeSH
• Bile Acids and Salts metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Carvedilol MeSH
• Membrane Transport Proteins MeSH
• Bile Acids and Salts MeSH