Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury.

Abstract

Oxidized low density lipoprotein (LDL), formed in vivo from presently unknown reactions, may play a role in atherogenesis. In vitro, transition metals such as iron and copper will facilitate LDL oxidation, but these metals are unlikely to exist in free form in normal body fluids. We have explored the possibility that LDL oxidation may be promoted by heme, a physiologically ubiquitous, hydrophobic, iron-containing compound. Indeed, during several-hour incubation, heme caused extensive oxidative modification of LDL; however, such modification requires only minutes in the presence of small amounts of HjO 2 or preformed lipid hydroperoxides within the LDL. Oxidative interactions between heme, LDL, and peroxides lead to degradation of the heme ring and consequent release of heme iron, which further accelerates heme degradation. Coupled (evidently iron-catalyzed) heme degradation and LDL oxidation are both effectively inhibited by hydrophobic antioxidants and iron chelators. That such hemin-induced LDL oxidation may be involved in atherogenesis is supported by the finding that LDL oxidized by hemin is extremely cytotoxic to cultured aortic endothelial cells. Overall, these investigations not only lend support to the idea that LDL oxidation by physiological substances such as heme may play a role in the process of atherogenesis but also may have broader implications, as similar oxidative reactions between heme and unsaturated fatty acids may occur consequent to hemorrhagic injury. (Arteriosclerosis and Thrombosis 1991;ll:1700-1711)

Haptoglobin Polymorphism and Association with Complications in Ghanaian Type 2 Diabetic Patients

“…Diabetic complications were strongly associated with Hp 2-2 and Hp 2-1, Hp 1-1, Hp 2-1 M, in a decreasing order in this study. The reasons for this could be due to (i) differences in Hb binding capacities of the different Hp phenotypes [47]; (ii) the shape and size of the Hp phenotypes [17]; (iii) an increase in redox active iron in the plasma of humans with the Hp 2-2 phenotype [48]; (iv) the ''clearance'' of Hp-Hb complex in the blood circulation after intravascular haemolysis by CD163 which is less effective in Hp 2-2 individuals [23]; and (v) the better antioxidant effects of Hp 1-1 phenotypes on low-density lipoprotein (LDL) oxidation than Hp 2-2 [49,50]. These may explain the susceptibility of Hp 2-2 individuals to complications such as coronary artery diseases (CAD), neuropathy, nephropathy and hypertension.…”

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

“…In vitro and in vivo, cells accumulate exogenous heme. This results in the synergistic amplification of damage and cytotoxicity of oxidants present in the cell [128,129].…”

Hemopexin counteracts systolic dysfunction induced by heme-driven oxidative stress

“…Heme promotes endothelial dysfunction by inducing the expression of adhesion molecules and reducing nitric oxide (NO) availability, which causes vasoconstriction [9][10][11][12][13][14]. Moreover, heme-derived ROS induce the proliferation of smooth muscle cells, that participate in vasculopathy associated with atherosclerosis and hypertension [15].…”