26Jan/17

Can Diet Help Improve Pulmonary Hypertension? An Insight from Inflammatory Bowel Disease Research

While reading a recent paper entitled “Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications” I experienced a feeling a remarkable familiarity… I felt as if I was reading a paper about endothelial dysfunction in Pulmonary Hypertension. It appears that endothelial cell (EC) dysfunction in both inflammatory bowel disease (IBD) and pulmonary hypertension (PH) are quite similar: the same mechanisms of dysfunction abound, the same proinflammatory molecules are released. There is proliferation, smooth muscle cell tone activation, platelet aggregation, hypoxia, eNOS downregulation, imbalance between vasodilators and vasoconstrictors, etc.  Even though this kind of makes sense (that pathology in a cell such as an endothelial cell could be quite similar regardless of what tissue/organ it occurs in), it nevertheless is quite interesting.… Read More...
31Dec/16

Pulmonary Edema in PH & PVOD – Potential Causes of PVOD Misdiagnosis

*DISCLAIMER: These are my own thoughts and opinions based on my research and are not meant to be taken as medical advice.* Below is a potential explanation for how edema could occur in Pulmonary Hypertension (PH) patients receiving vasodilator therapy, thus leading to them being potentially misdiagnosed for Pulmonary Veno-Occlusive Disease (PVOD)… It makes sense to think that because a PH patient does not respond to vasodilator therapy well, or experiences edema due to vasodilator therapy, it may be an indication that they have PVOD. The theory goes that vasodilators can “open” up the vasculature (even in PH patients) and if the veins are “occluded” or non-responsive/rigid, then there is a large pressure difference that occurs when the blood flows from the “open” to “closed/rigid” section causing backpressure and edema: “PAH-specific vasodilator therapies may cause an augmentation of pulmonary arteriolar blood flow against the fixed resistance of occluded pulmonary venules and veins.… 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...
09Aug/16

Thought Of The Day – Metabolism in PH, Heart v. Skeletal Muscle

Fatty acid oxidation is a slower but more energy producing process than glycolysis, but glycolysis is a much faster process. In slow twitch muscle fibers (predominantly present in marathon runners, for example), complete glucose and fatty acid oxidation occurs, but in fast twitch muscle fibers (predominantly present in sprinters, for example), glycolysis predominates.  Glycolysis is upregulated and present in the heart (myocardium), pulmonary vasculature, immune cells, and bone marrow progenitor cells in PH. Is the heart (which primarily relies on fatty acid oxidation) in PH switching to glycolysis to compensate (i.e. to build muscle to compensate for increased afterload)?  Or does the heart not need to do this, but is in glycolysis mode anyway, perhaps because of the sick lung circulation?… Read More...
05Aug/16

An Evolutionary Perspective On Macronutrient Profiles – A Case For Low Carb, Low Fat, and High Protein?

A thought experiment (and ONLY a thought experiment): If you think about it, when do we typically encounter something in this universe (in nature, or in the modern world) that requires a storage mechanism? Typically when the thing we encounter, the input, is rare, or when we anticipate that in the future, it will be rare or it will most likely be needed (an analogy is saving money in a bank)… Mother nature gave us storage mechanisms for things that were rarely encountered or for the anticipation that in the future, these stored things would most likely be needed. We have storage mechanisms for sugar (glycogen) and fat (triacylglycerol).… Read More...
02Aug/16

The Cholesterol Paradox, Part I

Here is the quote from the above diagram from Metabolic Regulation: A Human Perspective by Keith N. Frayn, regarding cholesterol regulation (emphasis added): “The full length SREBP protein is located in the ER. It is associated with the SREBP cleavage activating protein (SCAP), which “senses” the level of cholesterol, or related sterols, within the membrane of the ER. When the cholesterol content is low, the SCAP-SREBP complex migrates to the Golgi complex, where specific proteases cleave SREBP to release the N-terminal portion, “mature” SREBP. Mature SREBP moves to the nucleus where it binds to sterol response elements in the promoter regions of many genes.… Read More...
01Aug/16

Regulation of Mitochondrial Metabolism and PH

The following is an excellent excerpt from Metabolic Regulation: A Human Perspective, by Keith N. Frayn. After reading it, the connection between metabolism (specifically mitochondrial oxidative metabolism capacity) and PH should be clear. I’ll leave the in depth commentary of why (including how, if this is true, PH is restricted to affecting lungs as opposed to systemic circulation) for another post: “An important aspect of metabolic regulation and its adaptation to different circumstances is the use of oxygen to oxidize nutrients and, hence, generate ATP. There are two aspects relevant to this chapter. The first is a series of mechanisms that increase the ability of tissues to conduct oxidative metabolism.… Read More...
31Jul/16

The Pentose Phosphate Path and PH, Part I – RBCs, G6PD, & GSH

The pentose phosphate pathway (PPP) is a metabolic pathway that parallels glycolysis. In cells, within the cytosol, glucose is converted into glucose 6-phosphate (catalyzed by the enzyme hexokinase), which can then either 1) enter glycolysis (and subsequent glucose oxidation via citric acid cycle) to produce ATP, or 2) enter the PPP. The PPP (diagram below) is primarily an anabolic pathway; the primary purpose being the following: to produce molecules (specifically 5 carbon sugars, and Ribose-5-phosphate) used for fatty acid synthesis, nucleic acid synthesis, and protein synthesis. However, another important purpose of the PPP is to produce NADPH, a high energy electron carrier.… Read More...
31Jul/16

Thought Of The Day – AMPK, Pulmonary Vasculature & RV

Today’s thought stems from a quote I found reading Metabolic Regulation: A Human Perspective by Keith N. Frayn. This is one of my new favorite books… Quote: “AMPK senses energy status of the cell: when there is a drain on ATP, AMP rises and the AMPK is activated, leading in turn to inhibition of ATP utilizing pathways (particularly biosynthetic pathways) and activation of ATP-generating pathways (glucose uptake, glycolysis, fatty acid oxidation).” Thought: AMPK (5′ AMP-activated protein kinase) activation in some form, either via dietary means, or as a drug target, would seem to be a good idea for the pulmonary vasculature as it would potentially prevent proliferation of PASMC’s and PAEC’s, and perhaps even adventitial fibroblasts (because of the “preventing biosynthetic pathway” feature stated above).… Read More...