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...
12Mar/17

The Cholesterol Paradox, Part 3 – LDL in Heart Disease & Pulmonary Hypertension

There is more to LDL than meets the eye… While it is true that LDL is an established marker of cardiovascular disease risk, we need to be clear just how and why exactly this is so. First things first. LDL is a means for delivering cholesterol to tissues that need it (and all cells need cholesterol to survive). Cholesterol (and thus LDL) is necessary for life: it is involved in hormone synthesis (including sex hormones), cell wall synthesis and maintenance, and the synthesis of vitamin D and bile acids. Additionally, it is involved in the process of repairing cellular injury. Now to tackle a few myths… Myth #1 – LDL is the cause of Heart Disease While LDL is involved in the atherosclerosis process, it isn’t the driving force, the immune system is… Atherosclerosis is the result of an immune response, by definition you need a macrophage deposited in an arterial wall to initiate the process of atherosclerosis.… Read More...
10Feb/17

The Cholesterol Paradox, Part 2

This is part of a series of posts where I share and dissect information about cholesterol, the science behind cholesterol, and common fallacies surrounding cholesterol. Most of these posts are going to be short… where I just share bits of information that I’ve archived or that I’ve recently found, and some thoughts surrounding them. For Part I of this series, click here. For this post, I want to reflect on a quote from Metabolic Regulation: A Human Perspective by Keith N. Frayn (my emphasis added): “Perhaps surprisingly, the amount of cholesterol in the diet is not a major factor affecting the blood cholesterol concentration.… 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...
08Sep/16

Dr. Rhonda Patrick On Cell Metabolism, Cancer, And More…

I recently listened to this podcast between Robb Wolf, author of The Paleo Solution and one of my favorite nutrition researchers, and Dr. Rhonda Patrick, founder of Found My Fitness and yet another one of my favorite researchers. It was a great discussion about a wide variety of topics mostly revolving around cell metabolism. I’ve included a summary of the key points discussed below. Summary & Key Points: For healthy cellular function and healthy aging in general, you need metabolic flexibility Once a cell acquires so much damage to the genome, it becomes glycolytic The act of becoming glycolytic does not cause a cell to become cancerous – immune cells, fast twitch muscle fibers, and astrocytes are all glycolytic but not cancerous In cancer, the mitochondria are still working, they are just dysfunctional Cells are primed to die.… Read More...
06Sep/16

“Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung” – A Review

This is a review and summary of a recent paper entitled “Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung”. In this study, metabolomic profiling was used in an animal model of PH to try to identify biomarkers of early stage PH, in hopes of identifying a process to diagnose PH earlier. At the end of this post, I’ve included a chart summarizing all of the biomarkers found in the study. Some terms: MCT = Monocrotaline SMC = Smooth Muscle Cell EC = Endothelial Cell Summary & Key Findings In the MCT animal model, they observed metabolic changes in “multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis.” While less pronounced, the metabolic data derived from this study compared favorably with prior work carried out in humans with PH: “In support of our data in the MCT-exposed rat, PH patient metabolomic data also observed a significant elevation of glucose and fructose 6-phosphate levels [7].… Read More...
31Aug/16

Why “Starving Cancer” May Not Be So Bogus Of An Idea After All

It is well known that cancer cells switch their metabolism from a normal utilization of glucose and fats (glucose and fatty acid oxidation) to an abnormal, less efficient but more rapid, utilization of glucose. This abnormal utilization is referred to as glycolysis. When oxygen is not available, this is the pathway that is triggered.1 Glycolysis in itself doesn’t cause cancer per se, but it is a necessary consequence (i.e. necessary for cancer to develop). For example, our immune cells, red blood cells, cells lining the gut, and fast twitch muscle fibers, are all glycolytic, and they aren’t cancerous. They are glycolytic in order to rapidly proliferate (immune cells in response to infection, or gut cells to continuously be an effective barrier in the stomach), or in order to provide rapid energy when oxygen isn’t available in an adequate amount of time (e.g.… Read More...
30Aug/16

“AMPK modulates Hippo pathway activity to regulate energy homeostasis” – A Review

I’m on a YAP kick lately! This is another paper about the Hippo pathway and YAP but in relation to glucose homeostasis and cellular energy stress. In summary, the Hippo pathway is a tumor suppressor pathway. Energy stress, defects in glucose metabolism, and glucose starvation, all activate this pathway and decrease oncogenic downstream components (specifically YAP). The implications? Metabolic regulation and glucose homeostasis are integral pieces in the puzzle that is “What causes cancer?” Summary & Key Points: The Hippo pathway is a signaling pathway that is involved in the control of tissue and organ size in the body. Loss of the Hippo path components leads to tumor formation, which suggests that the Hippo path is crucial for suppressing tumors.… Read More...
26Aug/16

“Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension” – A Review

This was a very interesting and exciting paper that I discovered today via Pulmonary Hypertension News: “Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension”. I’m a large proponent of the hypothesis that metabolic dysregulation and immune dysfunction are key drivers in the development of pulmonary hypertension. This paper adds weight to my case that the former is most likely a key element in PH pathogenesis. I’ve also always believed that due to the enigmatic nature of the disease, and presence of “cancer”, “autoimmune”, and “metabolic dysregulation” like features, solving PH can potentially solve problems like cancer and autoimmunity. A few examples from the paper as it pertains to cancer: “Here, the identification of glutaminolysis as a mechanoactivated process coregulated with aerobic glycolysis advances our understanding of the regulatory hierarchy seen in the metabolic reprogramming in PH.… Read More...
24Aug/16

“Fatty acid metabolism in pulmonary arterial hypertension: role in right ventricular dysfunction and hypertrophy” – A Review

In the below I will be referencing and discussing quotes from the paper “Fatty acid metabolism in pulmonary arterial hypertension: role in right ventricular dysfunction and hypertrophy” by M. Talati. Basically, I’m distilling the key points that I’ve learned, summarizing them, and including any thoughts I may have. Overall it appears that the running thread through this paper is the following: Can metabolic syndrome or insulin resistance in PH cause RV dysfunction? Or is the dysfunction a result of PH? In sum, there is a dysregulation in fatty acid oxidation and glucose oxidation, with increased intracellular lipid accumulation, and an overall switch to glycolysis in the heart.… Read More...