Muscular adaptation to physical exercise has previously been described as a repair process following tissue damage. Recently, evidence has been published to question this hypothesis. The purpose of this study was to investigate inflammatory processes in human skeletal muscle and epimysium after acute physical exercise with large eccentric components. Three groups of subjects (n = 19) performed 45 min treadmill running at either 4 deg (n = 5) or 8 deg (n = 9) downhill or 4 deg uphill (n = 5) and one group served as control (n = 9). One biopsy was taken from each subject 48 h post exercise. Blood samples were taken up to 7 days post exercise. Compared to the control group, none of the markers of inflammation in muscle and epimysium samples was different in any exercised group. Only subjects in the Downhill groups experienced delayed onset of muscle soreness (DOMS) and increased serum creatine kinase activity (CK). The detected levels of immunohistochemical markers for T cells (CD3), granulocytes (CD11b), leukaemia inhibitory factor (LIF) and hypoxia-inducible factor 1β (HIF-1β) were greater in epimysium from exercised subjects with DOMS ratings >3 (0-10 scale) compared to exercised subjects without DOMS but not higher than controls. Eccentric physical exercise (downhill running) did not result in skeletal muscle inflammation 48 h post exercise, despite DOMS and increased CK. It is suggested that exercise can induce DOMS by activating inflammatory factors present in the epimysium before exercise. Repeated physical training may alter the content of inflammatory factors in the epimysium and thus reduce DOMS.

Objective-To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. Methods and Results-We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid-binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (Ͼ18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels. Conclusion-Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9. Key Words: circulating PCSK9 Ⅲ cholesterol synthesis Ⅲ LDL cholesterol Ⅲ diurnal rhythm Ⅲ growth hormone Ⅲ cholesterol-lowering drugs Ⅲ lipoproteins G enetic variants of proprotein convertase subtilisin kexin type 9 (PCSK9) influence plasma low-density lipoprotein (LDL) cholesterol in humans, accounting for both hypercholesterolemia and hypocholesterolemia and altered coronary risk. 1,2 PCSK9 modulates the number of LDL receptors (LDLRs) by triggering the degradation of LDLRs. 3 Gain-offunction mutations in the PCSK9 gene produce a phenotype of familial hypercholesterolemia, 1 whereas loss-of-function mutations reduce plasma LDL cholesterol levels. 2 Circulating PCSK9 is largely derived from the liver, 4,5 and plasma levels relate to the hepatic expression of PCSK9. 6 -9 It is still unclear to what extent PCSK9 is physiologically regulated and if such regulation may influence plasma LDL cholesterol levels in humans. Novel therapies aiming at lowering serum LDL cholesterol by interfering with PCSK9 activity are under development. 10 Fasting plasma levels of PCSK9 correlate positively with LDL cholesterol levels in healthy and diabetic patients 7,[11][12][13][14] ; however, in the most extensive study, 7 with Ͼ3000 subjects, PCSK9 levels only predicted 7% of the variation in LDL cholesterol. In animals, the hepatic gene expression of PCSK9 is partly under hormonal control: treatment with glucagon or high-dose estrogen reduces PCSK9 mRNA and increases the number of LDLRs, 15 whereas insulin 15,16 and growth hormone (GH) 17 both increase PCSK9 mRNA levels in rat liver.The gene expressions of PCSK9, the LDLR and 3-hydroxy-3-...

Introduction The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis (RA) on blood lipids oxidized low-density lipoprotein (oxLDL) and natural atheroprotective antibodies against phosphorylcholine (antiPCs).