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Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders-Interaction between the Heme Oxygenase and H2S-Producing Systems

期刊

出版社

MDPI
DOI: 10.3390/ijms22010047

关键词

oxidized hemoglobin; heme; vascular disease; hemorrhage; hemolysis; heme oxygenase; carbon monoxide; carbon monoxide-releasing molecules; hydrogen sulfide

资金

  1. Hungarian Academy of Sciences [11003]
  2. Hungarian Government [OTKA-K112333]
  3. European Union
  4. European Social Fund [GINOP-2.3.2-15-2016-00043, EFOP-3.6.2-16-2017-00006]
  5. Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary, within University of Debrecen [ED_181-2019-0028]
  6. Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary [TKP2020-NKA-04]
  7. [EFOP-3.6.3-VEKOP16-2017-00009]

向作者/读者索取更多资源

The study shows that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, including toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. The damage caused by oxidized hemoglobin and heme to cells and tissues is related to the pathological consequences of hemorrhage and hemolysis in humans.
Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H2S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H2S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic/hemorrhagic human diseases, and the potential beneficial role of CO and H2S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic/hemorrhagic diseases through heme oxygenase-1/CO as well as H2S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.

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