Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

TY - JOUR

T1 - Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells

T2 - A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

AU - Nitti, Mariapaola

AU - Furfaro, Anna Lisa

AU - Mann, Giovanni E.

PY - 2020/1/29

Y1 - 2020/1/29

N2 - Among antioxidants in the human body, bilirubin has been recognized over the past 20 years to afford protection against different chronic conditions, including inflammation and cardiovascular disease. Moderate increases in plasma concentration and cellular bilirubin generation from metabolism of heme via heme oxygenase (HMOX) in virtually all tissues can modulate endothelial and vascular function and exert antioxidant and anti-inflammatory roles. This review aims to provide an up-to-date and critical overview of the molecular mechanisms by which bilirubin derived from plasma or from HMOX1 activation in vascular cells affects endothelial function. Understanding the molecular actions of bilirubin may critically improve the management not only of key cardiovascular diseases, but also provide insights into a broad spectrum of pathologies driven by endothelial dysfunction. In this context, therapeutic interventions aimed at mildly increasing serum bilirubin as well as bilirubin generated endogenously by endothelial HMOX1 should be considered.

AB - Among antioxidants in the human body, bilirubin has been recognized over the past 20 years to afford protection against different chronic conditions, including inflammation and cardiovascular disease. Moderate increases in plasma concentration and cellular bilirubin generation from metabolism of heme via heme oxygenase (HMOX) in virtually all tissues can modulate endothelial and vascular function and exert antioxidant and anti-inflammatory roles. This review aims to provide an up-to-date and critical overview of the molecular mechanisms by which bilirubin derived from plasma or from HMOX1 activation in vascular cells affects endothelial function. Understanding the molecular actions of bilirubin may critically improve the management not only of key cardiovascular diseases, but also provide insights into a broad spectrum of pathologies driven by endothelial dysfunction. In this context, therapeutic interventions aimed at mildly increasing serum bilirubin as well as bilirubin generated endogenously by endothelial HMOX1 should be considered.

KW - atherosclerosis

KW - bilirubin

KW - diabetes

KW - endothelial cells

KW - HMOX1

KW - hypertension

KW - obesity

KW - tumor

UR - http://www.scopus.com/inward/record.url?scp=85079508519&partnerID=8YFLogxK

U2 - 10.3389/fphys.2020.00023

DO - 10.3389/fphys.2020.00023

M3 - Review article

AN - SCOPUS:85079508519

SN - 1664-042X

VL - 11

JO - Frontiers in Physiology

JF - Frontiers in Physiology

M1 - 23

ER -