Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea.
Bulmer AC , et al.
«Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.»
atherosclerosis, heart, heme oxygenase, hepatic, lipid
Endothelial dysfunction contributes to the early stages of atherosclerosis
, whereby 97 expression of adhesion molecules and oxidant generating NADPH
oxidase (NOX) draws 98 leukocytes to sites of injury/lipid accumulation, propagating vascular injury and encouraging 99 vascular smooth muscle
proliferation and neointima formation. Increased
NOX driven 100 reactive oxygen species
) production and intimal thickening contribute to hypertension
101 and impaired vasodilatation, involving sequestration of released nitric oxide
. Based upon its 102 ROS
properties, it is hypothesized that bilirubin
has the potential to 103 reduce
Mild hyperbilirubinaemia as an endogenous mitigator of overweight and obesity: Implications for improved metabolic health.
Seyed Khoei N , et al.
«RESULTS: BMI, hip circumference (HC), and lipid profile were significantly lower in GS. UCB was inversely correlated with BMI (p <0 .001), HC as well as with fat mass (FM) and lipid variables (p < 0.05). Moreover, DM2 patients had significantly lower UCB compared to GS and healthy controls. Older GS subjects (≥35 years) had significantly reduced anthropometric data and improved lipid profile.
CONCLUSIONS: Our results propose that the health promoting potential of mild hyperbilirubinaemia may extend to protection from age-related weight gain and dyslipidaemia.»
Anthropometric data, Bilirubin, Cardiovascular disease (CVD) risk factors, Lipid profile, Overweight/obesity, Unconjugated bilirubin (UCB)
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Relationship between unconjugated hyperbilirubinemia and lipoprotein spectrum.
Očadlík I , et al.
«RESULTS: We found significantly higher levels of total bilirubin and unconjugated bilirubin in patients with Gilbert's syndrome. In the control group, probands had significantly higher triglycerides levels, VLDL cholesterol levels, IDL cholesterol level, and small dense LDL levels compared to the group with Gilbert\'s syndrome. Probands with Gilbert's syndrome had significantly lower presence of atherogenic lipoprotein spectrum than probands in control group (5% vs. 18%). We found significantly negative correlation between serum unconjugated bilirubin levels and LDL 3-7 (r = - 0.594, p <0.01), as well as between bilirubin and triglycerides (r = -0.540, p<0.01). Serum bilirubin concentration and LDL 1-2 concentration correlated significantly positively (r = 0.451, p <0.05).
CONCLUSION: The presence of atherogenic lipoprotein spectrum is determined by the particular representation of small dense LDL. Atherogenic spectrum was presented significantly less in patients with Gilbert\'s syndrome compared with the control group (5% vs. 18%). In our study, we have not followed the risk of coronary heart disease or other manifestations of atherosclerotic arteries disability. However, we found the inverse relationship of serum bilirubin levels and atherogenic small dense LDL. We found out that the protective antiatherogenic effect of hyperbilirubinemia is potentiated by low occurence of strongly atherogenic small dense LDL and persons with byperbilirubionemia (in our case represented Gilbert's syndrome), could be protected against the development of atheroscleosis.»
Adolescent, Adult, Atherosclerosis, Bilirubin, Blood Protein Electrophoresis, Cholesterol, Female, Gilbert Disease, Humans, Hyperbilirubinemia, Lipoproteins, Lipoproteins, LDL, Lipoproteins, VLDL, Liver Function Tests, Male, Middle Aged, Risk Factors, Triglycerides, Young Adult
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