08Aug/17

Inflammation in Pulmonary Hypertension – A Scientific Perspective, with a focus on Hypoxic PH

What is inflammation? Inflammation is a complex biological response of the body to remove foreign objects like pathogens (bacteria, virus, fungus), damaged cells, or irritants. It involves cells of the immune system, blood cells, tissue cells, and chemical mediators such as cytokines, chemokines, and reactive oxygen species. We typically have negative connotations associated with inflammation, which is justified, but not all cases of inflammation are negative. We need inflammatory processes to remove harmful pathogens, damaged cells or irritants. The problem arises when this inflammation goes unresolved, and becomes a chronic condition. There is another common harmful side of the immune system, however.… Read More...
26Oct/16

“A proteomic approach to altered innate and adaptive immunity in the pathogenesis of PAH” – A Synopsis

Below is a synopsis of “A proteomic approach to altered innate and adaptive immunity in the pathogenesis of PAH”, a talk by Marlene Rabinovitch (MD, Stanford) given at the Vera Moulton Wall Center for Pulmonary Vascular Disease (video below). It is one of my favorite talks so far in this series of lectures… Hypothesis: there is an abnormal immune response (both innate and adaptive) affecting pulmonary arteries that is common in all forms of PAH Altered adaptive immunity in PAH pathogenesis What if antigens produced in lung are the site for autoantibody formation and immune complex deposition directly in the lung and in the perivascular area?… Read More...
22Sep/16

Lectins, Tissue Transglutaminase, & PH

As per this talk by Robb Wolf at UCSF (at ~1 hour in), non-Western Huntington’s disease carriers don’t seem to express the disease. Since Huntington’s Disease is a rare genetic neurodegenerative disease, this is intriguing and suggests that the expression of the disease may be epigenetic. As he points out a few minutes later, tissue transglutaminase has been implicated in Huntington’s Disease. What does this have to do with epigenetics and PH? Tissue transglutaminase is an enzyme that is responsible for modifying most of the body’s proteins. A key tenant of the “Paleo Diet” and similar metabolic/nutritional therapies is that consumption of dietary lectins found in grains and legumes play a role in the development of a variety of diseases by escaping into the bloodstream from the gut and triggering immune responses as well as interacting with the enzyme tissue transglutaminase.… Read More...
13Aug/16

Pulmonary Hypertension – Atherosclerosis of the Lungs?

The passage below is from “Metabolic Regulation: A Human Perspective”, by Keith N. Frayn. I sometimes read things with a “PH filter” (and sometimes with a more global filter depending on context), and this particular passage was read with my “PH filter”… It got me thinking about the relationship of elevated non-esterified fatty acid concentrations in the plasma, adipose tissue, atherosclerosis, and if there is any connection between those and pulmonary hypertension. For some perspective, fatty acid metabolism is dysregulated in PH patients, with decreased fatty acid oxidation in myocardium and potentially increased lipid accumulation in myocardium and other tissues, increasing risk of lipotoxicity.… Read More...
08Aug/16

“Regulation Of Pulmonary Macrophage Function In Health And Disease” – A Synopsis

Below is a video and synopsis of the talk “Regulation Of Pulmonary Macrophage Function In Health And Disease” by Dr. Bruce Trapnell at the Vera Moulton Wall Center for Pulmonary Vascular Disease: Summary GM-CSF is important for macrophages to clear adenovirus transfections Normally, an adenovirus exits the endosome and is targets the nucleus of the cell and dumps its DNA into the nucleus In cells, GM-CSF redirects adenovirus to lysosomes via PU.1 GM-CSF receptor has pleiotropic effects on macrophages: low concentrations of GM-CSF leads to signaling that induces differentiation and survival of macrophages, and at higher concentrations, that pathway is shut down and another pathway occurs through the receptor that leads to growth and priming functions as well as survival.… Read More...
04Aug/16

“Novel Insights Into Lung Autoimmunity Through Research In Rare Mendelian Diseases” – A Synopsis

This is a video by Dr. Anthony Shum from an excellent series of talks by the Vera Moulton Wall Center for Pulmonary Vascular Disease (a brief summary of which is below): Summary Exome sequencing (similar to what 23andMe does) can provide insight into rare Mendelian diseases. Specifically, Dr. Shum has used this to analyze patients with autoimmune interstitial lung disease patients (typically patients who present at a young age, have pulmonary hemorrhage, arthritis, and presence of the autoantibodies ANCA and ANA) and has found that they all contain a mutation in the COPA gene, which was predicted to be damaging. COPA is ubiquitously expressed, and enables protein transport between the Golgi Apparatus and the ER.… Read More...