Relationship Between Bilirubin Concentration, Coronary Endothelial Function, and Inflammatory Stress in Overweight Patients

Yoshino, Satoshi; Hamasaki, Shuichi; Ishida, Susumu; Kataoka, Tetsuro; Yoshikawa, Akiko; Oketani, Naoya; Saihara, Keishi; Okui, Hideki; Shinsato, Takuro; Ichiki, Hitoshi; Kubozono, Takuro; Kuwahata, So; Fujita, Shoji; Kanda, Daisuke; Nakazaki, Mitsuhiro; Miyata, Masaaki

doi:10.5551/jat.6346

Cited by 40 publications

(43 citation statements)

References 47 publications

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“…Estos hallazgos han sido replicados en diversos grupos étnicos 41 . Se postula que la bilirrubina ejerce un efecto protector antioxidante y/o antiinflamatorio 42 . La bilirrubina tiene mayor capacidad en reducir la oxidación lipídica que el glutatión y la vitamina E 43,44 .…”

Section: Discussionunclassified

Prevalencia de síndrome de Gilbert y sus determinantes genéticas en población chilena

et al. 2013

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Section: Discussionunclassified

Prevalencia de síndrome de Gilbert y sus determinantes genéticas en población chilena

et al. 2013

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“…Moraes et al (112) also showed that the endogenous HO-derived by-products (bilirubin, biliverdin, and carbon monoxide) suppressed the prooxidant effect of heme and the proliferation of VSMC via modulation of NADPH oxidase activity. Moreover, higher serum bilirubin concentrations are also independently and positively correlated with improved FMD in overweight Japanese patients (197), and a negative relationship between bilirubin levels and incidence of hypertension is reported in a Korean population (26). In the latter study, subjects with lower bilirubin levels (Ͻ1.1 mg/dl) had higher mean arterial pressures and serum creatinine concentrations after adjustment for confounders.…”

Section: Potential Protective Effects Of Bilirubinmentioning

confidence: 94%

“…Flow-mediated dilation was significantly greater in overweight patients with the greatest bilirubin concentrations (Ͼ0.77 mg/dl), further suggesting that bilirubin protects against endothelial dysfunction (197). Elevated serum bilirubin concentrations are also associated with improved endothelium-dependent function of coronary arteries in patients without coronary heart disease (CHD) (196).…”

Section: Potential Protective Effects Of Bilirubinmentioning

confidence: 98%

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

Boon

Bulmer

Coombes

et al. 2014

American Journal of Physiology-Renal Physiology

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Unconjugated bilirubin is an endogenous circulating antioxidant, bound to albumin, and therefore is retained in the vascular compartment. Bilirubin has well-documented neurotoxic effects in infants; however, current evidence indicates mildly elevated bilirubin is associated with protection from cardiovascular disease and all-cause mortality in adults. Recent clinical studies show mildly elevated bilirubin is associated with protection from kidney damage and dysfunction, in addition to cardiovascular events and all-cause mortality in patients undergoing hemodialysis. This is the first review to examine the clinical evidence and summarize the potential mechanisms of action that link bilirubin to protection from kidney damage, subsequent kidney failure, and dialysis-related mortality. With this understanding, it is hoped that new therapies will be developed to prevent renal dysfunction and mortality from cardiovascular disease in at-risk individuals.

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“…Investigations in GS subjects, and experiments utilizing the rat model of hyperbilirubinaemia (Gunn rat), show protection from ex vivo [9,10] and in vivo [11] oxidation, coronary atherosclerosis [12], protection from thiol and protein oxidation [13] as well as anti-inflammatory [14] or anti-proliferative properties [15,16] of bilirubin.…”

Section: Introductionmentioning

confidence: 99%

Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilbert's syndrome

et al. 2013

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Recent epidemiological and clinical data show protection from CVD (cardiovascular disease), all-cause mortality and cancer in subjects with GS (Gilbert's syndrome), which is characterized by a mildly elevated blood bilirubin concentration. The established antioxidant effect of bilirubin, however, contributes only in part to this protection. Therefore we investigated whether mildly elevated circulating UCB (unconjugated bilirubin) is associated with altered lipid metabolism. The study was performed on GS and age- and gender-matched healthy subjects (n=59 per group). Full lipoprotein profile, TAG (triacylglycerols), Apo (apolipoprotein)-A1, Apo-B, lipoprotein(a), the subfractions of LDL (low-density lipoprotein) and selected pro-inflammatory mediators were analysed. A hyperbilirubinaemic rodent model (Gunn rats, n=40) was investigated to further support the presented human data. GS subjects had significantly (P<0.05) improved lipid profile with reduced total cholesterol, LDL-C (LDL-cholesterol), TAG, low- and pro-atherogenic LDL subfractions (LDL-1+LDL-2), Apo-B, Apo-B/Apo-A1 ratio and lower IL-6 (interleukin 6) and SAA (serum amyloid A) concentrations (P=0.094). When the control and GS groups were subdivided into younger and older cohorts, older GS subjects demonstrated reduced lipid variables (total cholesterol and LDL-C, TAG and LDL-C subfractions, Apo-B/Apo-A1 ratio; P<0.05; Apo-B: P<0.1) compared with controls. These data were supported by lipid analyses in the rodent model showing that Gunn rat serum had lower total cholesterol (2.29±0.38 compared with 1.27±0.72 mM; P<0.001) and TAG (1.66±0.67 compared with 0.99±0.52 mM; P<0.001) concentrations compared with controls. These findings indicate that the altered lipid profile and the reduced pro-inflammatory status in hyperbilirubinaemic subjects, particularly in the older individuals, probably contribute additionally to the commonly accepted beneficial antioxidant effects of bilirubin in humans.

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Relationship Between Bilirubin Concentration, Coronary Endothelial Function, and Inflammatory Stress in Overweight Patients

Cited by 40 publications

References 47 publications

Prevalencia de síndrome de Gilbert y sus determinantes genéticas en población chilena

Prevalencia de síndrome de Gilbert y sus determinantes genéticas en población chilena

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilbert's syndrome

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