Genetics, Oxidative Stress and Endothelial Growth
Today’s snippet article only just touches on the subject of genetics. This is a field often beyond what most practitioners and chamber personnel need to be concerned with. It is interesting science though. As we know genetic expression underlies biological function. Things like transcription factors and proteins which trigger genetic regulation are what drive whether a gene is “switched on” or “switched off”. In medical terms this is referred to as being upregulated or down-regulated. It’s these genes that direct the physiological processes responsible for healing, cell growth and proliferation, new blood vessel growth (angiogenesis), osteoclast formation in bone healing, fibroblast formation in wound healing, collagen release and many, many more factors discussed across many of the articles published here.
The subject of today’s discussion is a paper published in the Journal of Surgical Research in 2011 by Lawrence Hightower of the University of Connecticut, Emeritus Professor of Molecular and Cell Biology, and is entitled:
The paper is nothing less than a full blown science alert for those who enjoy the science. It doesn’t simply cite other primary and secondary sources, it presents raw original data directly from experiments performed. This is the meat and potatoes of proof so to speak. The tables and diagrams are representations of how specific genes responded during experimentation.
The paper summarizes:
“In summary, we find that HBOT activated the expression of cytoprotective and growth-promoting genes in endothelial cells. This response was dependent on elevated pressure, indicating that high concentrations of dissolved oxygen were required to induce these responses. In Addition, HBOT was found to enhance endothelial cell vascular network formation, particularly after two successive treatments.”
It also concludes:
“Our data confirm that HBOT can induce cell growth in microvascular endothelial cells and point to the subunits of the AP-1 transcription factor as playing a role.”
“With regard to endothelial cell protection, pathway analysis pointed to the Nrf-2 oxidative stress response pathway as being an important pathway regulated by HBOT. This pathway controls the expression of over 200 protective and antioxidant genes (Suh et al. 2004; Nguyen et al. 2009;Zakkar et al. 2009)“
The paper concludes that transcription factors for the initiation and proliferation of cells and repair process in endothelial growth are upregulated by exposure to elevated pressures of oxygen over simple administration of oxygen at normal pressure, pressure being key.
Endothelial cells are those which line the walls of blood vessels and are integral in the formation of new blood vessels, without which accelerated wound healing would not be possible.
Wound healing with or without HBOT relies on the formation of new blood vessels into the site of the wound for delivery of oxygen which then supports the formation of tissue scaffolds, collagen release, tissue granulation and so on. HBOT is proven here to upregulate the genes responsible for this particular cells proliferation supporting wound healing, especially wound healing in wounds that are compromised and unable to develop new vasculature in the normal wound healing sequence of hemostasis, inflammatory, proliferative and maturation stages.
What the paper also concludes is that cells become resistant to oxidative stress. This supports the position that oxygen toxicity is not quite as prohibitive as it is often portrayed to be as discussed in our 3 part series on the subject to be found here. Yes, a balance needs to be struck between enough and too much oxygen, but toxicity should not be a reason to completely exclude HBOT as a potential treatment. That balance is almost always within the limits of common treatment protocols. This is incidentally and unfortunately the position of many medical professionals and accordingly they dismiss HBOT as a potential treatment to the detriment of the patient. Unfortunately the information they cite is outdated as shown in this, and many other studies.
HBOT upregulates the genes responsible for protecting against “lethal oxidative stress” at the cellular level.
Further, the protein metallothionein is upregulated affecting this outcome. This means that cells don’t suffer permanent damage from oxidative stress since the HBOT that is reported to cause such oxidative stress is also responsible for the protection of cells against toxicity by mechanism of upregulation antioxidant factors. Paradoxical yes, but conclusive nonetheless.
The experiments presented here support the position that HBOT accelerates endothelial growth which is the basis of wound healing and the rationale behind the administration of HBOT for this purpose.
Certainly a good read for the science folk.