Cholesterol Lipid Hypothesis Part V - Endothelial Dysfunction
February 10, 2020
How does an artery clog?
Recap: In an obese person, we have a scenario where a fat cell has been stuffed by dietary sugar excess and the cell membrane is damaged by oxidized free fatty acids, FFA, making it an immune reactive adipocyte that is releasing pro-inflammtory chemicals systemically. As the lipoproteins increase in the blood stream to compensate for the excess FFA and LPS, a concentration gradient forms allowing a small dense LDL particle to slip into the heart vessel wall where it can be oxidized and engulfed by a professional macrophage forming a foam cell. If the foam cell is not appropriately cleared because of the chronic systemic inflammatory lipid onslaught, you have the nidus for an inflamed area that has invaded in the artery wall.
Thus, I believe that the inflammation is the major driver of persistent damage to the heart vessel not the cholesterol itself.
Other than direct food induced inflammatory reactions, what else is contributing to the inflammation here? My personal favorite is the abnormal microbes that inhabit your gut. In previous lectures I showed that the standard American diet loaded with refined sugar and dysfunctional fats promote the wrong types of bacteria to grow in the gut. This fact is well known and the evidence keeps mounting that the gut is ground zero for all inflammatory human issues. Gram negative rod bacteria like e. coli are one such class that proliferates on the SAD diet. When these bacteria die off they release an irritating cell wall compound called a lipopolysaccharide or LPS for short. This bacterial cell wall debris is recognized by the immune system's innate toll like receptors triggering an inflammatory response locally if they are not cleared. The persistence of the dysfunctional gut bacterial cell wall debris can induce a low grade systemic inflammation called low grade endotoxemia. It has also been shown to induce inflammation causing insulin receptor damage and type 2 diabetes, the number one risk factor for a heart attack! (Cani P. et. al. 2007)(Cani P. et. al. 2018)(Kasselman L. et. al. 2018)
For those inclined to research this topic further, the 2018 GUT article by Dr. Patrice Cani is a tour de force in all things microbiome.
What I am saying here is that not only does our poor food choices directly effect the genesis of heart disease, but also drives further inflammation by altering the composition of our microbiome toward a low grade systemic inflammatory type.
Remember from two weeks ago that the lipoproteins like LDL carry these bad bacterial boys to the liver for detoxification and clearance. However, when the lipoproteins get oxidized and glycated by chemical exposure, poor dietary choices or oxidative stress they become less functional and have reduced innate immune clearing capacity further increasing inflammation and likely causing more lipoproteins to be developed to deal with the bacterial burden.
Remember that diabetes and smoking are two of the greatest risk factors for a heart attack. The common link to these two factors is that they both induce profound inflammation in the system. Smoking does it by chemically altering our cells. Diabetes does it by keeping the glucose level in the blood stream too high and promoting excessive free fatty acids which induces protein fat sugar coupling and oxidation that is pro-inflammatory to the immune system.
This process occurs over years as the immune system continues to fight the good fight in the gut and blood stream as the human offender continues to stuff fat cells with sugar, flour and bad fats or smoke daily. It unfortunately is a losing battle. This is not an exhaustive list as it has been shown that air pollution, toxic exposures, sedentary behavior and stress among others also are triggers for inflammation.
Somewhere along this progressive continuum the heart vessel in susceptible individuals develops a plaque of hardened and calcified fat that starts to block the vessel. When this plaque ruptures based on an acute stress, then platelets come to clot the damage and occlude the vessel causing the flow of oxygenated blood to not reach the heart muscle. This causes the heart muscle cells to die, i.e. a heart attack.
If the vessel is a major source of blood to the heart muscle, you can suffer an infarction that prevents the heart from being able to pump and you are unfortunately dead.
I have been asked why a pediatrician is focusing on a heart attack when they never occur in kids. The answer is that most disease of adulthood can be prevented if we teach our kids this truth.
I know that I have simplified this complex topic down to a few major problems. There are genetic outliers on both sides of this spectrum, however, for the vast majority of us, the consumption of refined flour, sugar, trans fats, oxidized PUFA's, exposure to chemicals and toxins are likely the root cause of our coronary artery disease risk.
If we look for a population that has little to no heart disease, the Tsimane Indians of Bolivia are one such group. When this population was studied they were noted to have no significant heart disease. Why? Is it genetic protection or a lifestyle difference? Most likely, the answer is that they are not exposed to poor quality foods, chemicals and stressors in general. The authors state: "Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity." (Kaplan H. et. al. 2017)
The only paradox here is that the Tsimane Indians had a high CRP, c reactive protein, which is a nonspecific marker of systemic inflammation used in predicting heart attacks in western civilized countries. This was due to infectious disease burdens from parasites and other indigenous diseases and wholly unrelated to how we in the west use the CRP. Westernized inflammation is due to damaging lifestyle choices that lead the immune system to attack self, whereas the Tsimane Indian's inflammation is due to the fact that the immune system is busy fighting pathogens in their environment which is protective of self. This truth is also shown in the volume of autoimmune diseases in western cultures versus third world environments.
Where does this diatribe leave us?
Next week: what is the recipe for success?
Molecular Biology of the Cell. 4th edition. Alberts B.
Deep Nutrition, Shanahan C.
Slauch J. Molecular Microbiology Article
Spiteller D. Angew Chem Int Ed Engl Article
Valledor Wiley Article
Gotto Trans Am Clin Climatol Assoc Article
Kromhout Acta Cardiology Article
Glass Cell Metabolism Article
Kaplan Lancet Article
Kasselman Atherosclerosis Article
Cani Diabetes Article
Cani Diabetes Article 2008
Cani Gut Article