INFLAMMATION PART 7 ENDOTHELIAL DYSFUNCTION continued

NITRIC OXIDE THE KEY TO ENDOTHELIAL HEALTH

From the image to the left (also in last weeks blog, figure 10) the endothelium acts as a brain regulating dozens of vital functions every second. Recall angiotensin II is on the right side and nitric oxide (NO) is on the left side of the see saw. One of the keys to maintaining a normal, vibrant, and healthy endothelium lies in maintaining a plentiful supply of nitric oxide (NO). If the endothelium is the brain of the blood vessel then nitric oxide (NO) is the fuel for that brain.

Nitric Oxide, NO, is a short-lived, endogenously produced gas that acts as a signaling molecule in the body. Signal transmission by a gas, produced by one cell, which penetrates membranes and regulates the function of other cells is an entirely new principle for signaling in the human organism. The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, has awarded the Nobel Prize in Physiology or Medicine for 1998 to Robert F Furchgott, Louis J Ignarro and Ferid Murad for their discoveries concerning “the nitric oxide as a signaling molecule in the cardiovascular system.^[1]

Nitric oxide increases blood vessel dilation and blood flow, decreases the adhesion of monocytes to the endothelium, decreases blood clotting, and prevents the oxidation of LDL.^[2]

Wow, did you just catch that? Nitric oxide (NO) is a pretty important molecule as you can see from the above quote. NO is an amazing neurotransmitter gas which was only recently discovered in 1998. Your endothelium has its work cut out. It needs to balance dozens of hormones like angiotensin II against NO on a second to second basis while “thinking” about all kinds of other things. It’s a very busy endocrine organ. It’s the blood vessel’s computational computer, a multitasking midget. Yet, have you ever heard of it on Junk Food TV? That’s nuts because this is the one “organ” that you really must keep well nurtured. When this baby goes south your body is in a world of hurt-silent hurt. Once you start harming it with convenience foodstuffs, and toxic chemicals you create the worst, yet most fundamental, imbalance I discuss in this book. When it starts to become injured or technically speaking “activated” you start to see a drop in the synthesis of NO. The endothelial cell also produces angiotensin II (AII) to counteract vasodilation. Angiotensin II is a big player that has the exact opposite effect from NO, it causes vasoconstriction. When the endothelium becomes imbalanced in favor of AII it can contribute to hypertension and promote inflammation. This is where you, for example, see a synergistic effect with obesity: fat cells produce excessive quantities of angiotensinogen which becomes angiotensin II magnifying the chances of developing hypertension. You could say that NO (on the left side figure 10) is in constant equilibrium with AII production (on the right side) for proper homeostasis. However, all that is necessary for AII to be dominant is that there is a relative decrease in NO availability. Without NO you see the balance tip to the right in favor of potentiating disease states like hypertension.

It may turn out, as some researchers have suggested, that the final common pathway for diabetes, some forms of dementia including Alzheimer’s disease, heart disease, stroke, peripheral vascular disease and other conditions is endothelial activation. The typical American lifestyle drives this process in a vicious cycle of never ending inflammation and oxidation.

HYPERTENSION-THE WARNING

Add the tincture of time with continuous, non-stop, stressors like a stressful, unhappy work place, poor quality sleep, anger, fast food, you know, all of the things that I was experiencing right before my fateful evening. It’s nothing new, just the usual stuff we Americans like to do to ourselves, and before you can say “whadidyasay,” you start to see the early damage reports arriving on your desk. That often starts with the diagnosis of hypertension. Your diagnosis of high blood pressure should be viewed as a big, red-flag event. It’s the warning shot fired over your head to stop running reckless. It indicates very clearly that you have now entered a powerful state of dis-ease with a sickened endothelium.

This endothelial dysfunction paves a yellow brick road but this one isn’t going to the Land of Oz where you might encounter happy, fluffy animals and tiny, presumably healthy, humans. Like strolling through a diseased aorta, the yellow bricks on this road are plaques, and the path leads to the Land of Anguish. Endothelial inflammation is one of the uniting causative factors in a hundred first-world diseases. Keeping NO in plentiful supply acts as an antidote to endothelial dysfunction, oxidation and inflammation:

NO apart of being a vasodilator,… reduces platelet aggregation, tissue oxidation, tissue inflammation, activation of thrombogenic [tendency toward clotting] factors, cell growth, proliferation and migration, also it inhibits proatherogenic and pro-inflammatory cytokines expression and it favors fibrinolysis… All these factors reduce atherogenesis and its complications. For this reason NO is considered the antiatherogenic molecule.^[3] [Emphasis mine]

Therefore we need to do everything we can to generate as much NO as possible at all times to remain healthy. Simple really. Sadly, in the land of the free, pounding your endothelium into submission is far easier than nurturing it. Virtually everything we like to do in the workplace or for leisure harms our endothelium. The typical American diet and lifestyle tends to produce a state of decreased NO production by routinely injuring endothelial cells. Over time we generate a pathologically imbalanced system ripe for disease. Chronic endothelial dysfunction leading to hypertension is a guaranteed side effect when we pursue “convenience” over all else.

HIGH-CARB, OMEGA 6 FEASTS STILL ENDORSED

It’s surprisingly easy to hurt your endothelium as a first world resident. We now know that many conditions cause endothelial activation such as the classic cardiovascular risk factors plus the many new, emerging risks. All of these “risk factors” and many more share a common effect by generating oxidative stress and reactive oxygen species (ROS). It’s really interesting that so far no mainstream medical text, website, or publication will list high Ω6 PUFA intake, and high carbohydrate diets as risk factors for atherosclerosis when these two are some of the worst offenders I can think of. More proof lies in the fact that the incidence of heart disease is actually increasing in spite of millions of statin users following the AHA high-carb dietary plan.

DARN VIKINGS ARE PILLAGING THE AHA DIETARY GUIDELINES

Meanwhile Sweden as of 2014 has become the first Western nation to wake up and develop national dietary guidelines that reject the popular low-fat diet dogma in favor of low-carb, high-fat nutritional advice.

The switch in dietary advice followed the publication of a two-year study by the independent Swedish Council on Health Technology Assessment. The committee reviewed 16,000 studies published through May 31, 2013.

Swedish doctor, Andreas Eenfeldt, who runs the most popular health blog in Scandinavia (DietDoctor.com) published some of the highlights of this study in English:

Health markers will improve on a low-carbohydrate diet:

…a greater increase in HDL cholesterol (“the good cholesterol”) without having any adverse affects on LDL cholesterol (“the bad cholesterol”). This applies to both the moderate low-carbohydrate intake of less than 40 percent of the total energy intake, as well as to the stricter low-carbohydrate diet, where carbohydrate intake is less than 20 percent of the total energy intake. In addition, the stricter low-carbohydrate diet will lead to improved glucose levels for individuals with obesity and diabetes, and to marginally decreased levels of triglycerides.” ^[4]

In the press release referring to the above study entitled Dietary Treatment for Obesity, heavy cream, bacon and butter are all considered safe to eat in direct contradistinction to the American Heart Association’s guidelines. Once again they both can’t be right. I’ll go with the Swedish expert committee on this one. After all, what agenda would they have? The Swedish Council on Health Technology Assessment is independent so we can assume it’s not like the corrupted, paid off, agencies here in America where no advice on bone health, sugar, cholesterol, saturated fat, sunlight exposure, vitamin D, statins, heart health, depression, and cancer prevention can be taken at face value.

It appears the Swedish authorities are doing what decent people do. They are giving advice based on real, scientific, conclusions in an effort to save lives just like I’m trying to do-something you will not see in America. But that’s fine if they want to play that way in the US. In my SMD I allow up to 30% of your daily calories to be obtained eating safe carbohydrates but I stress that most will do better with 20%. I would also add that based on my personal experience, and several good studies, triglycerides substantially decrease with a 20% or less carbohydrate diet. Yet they plummet when you add pharmaceutical grade high-dose fish oil to the program. Even at the upper limit of 30% safe carbs we are still literally half the carbs the AHA recommends. As you can see the Swedes passed the mental status exam indicating that they are in fact perfectly sane in a world gone insane. They are in agreement with my suggestions.

OXIDATIVE STRESS

Normally the body has powerful free radical “mops” that are designed to prevent oxidative damage such as super oxide dismutase, glutathione peroxidase, and catalase. When these systems are overwhelmed and the endothelium sickens,

…cardiovascular disease has the perfect opportunity to develop. All the experience obtained in the last years, suggests that… endothelial dysfunction is responsible for all the plaque growth, differences in plaque development and plaque characteristics. For all these reasons, endothelial dysfunction is one of the principal mechanisms in atherosclerotic disease.^[5]

Once endothelial activation occurs, reactive oxygen species (ROS) are generated like hydrogen peroxide (H2O2) that promotes the evolution of foam cells. NO production from within the endothelial cells decrease from the continuing development of ROS leaving the endothelial cells themselves damaged, eventually dying, and falling off their basement membrane. If this continues a porous opening for the recruitment of oxLDL develops on the endothelium like in the Apian Way example. Like a law of physics the atheroma develops from this condition.

One of the body’s defenses is to contain the atheroma within a fibrous cap. The cap however will degenerate if the provocative stimuli, the ROS are not quenched. If left to its own devices, oxidative stress continues as it weakens the atheromatous (plaque) cap to finally cause plaque rupture, thrombogenesis (blood clot formation), and a heart attack. Oxidative stress is present as a major component of the inflammatory response.

“Now we know that the pro-oxidant state is present in all stages of atherosclerosis from the beginning to the acute thrombotic event.”^[6]

Once again, this means that we must be aware of what generates free radicals in our bodies and what we can do to arrest this process. Remember that the risk factors we talk about all tend to amplify one another. This leads to a toxic synergy or more correctly a toxic dysergy where the sum total damage far exceeds the individual harms added up separately. Each risk factor like diabetes or the metabolic syndrome acts as a fuel on the endothelium’s fire in the same way that kerosene, diesel fuel, or gasoline act when poured on a fire. They are all different accelerants but they all promote combustion. In a similar fashion the risk factors or I should say the Irritating Agents (IA) for atherosclerosis are many and varied. They all promote endothelial dysfunction, the generation of ROS, uncontrolled oxidation and stimulation of the immune response.

In short it’s free radical formation and oxidation which drives the process just like we discussed when generating oxLDL. Any number of IA mentioned above can either directly injure the endothelium or damage the LDL particle or both. This process continues unabated as long as there is continuous stimulation to further oxidation and free radical production. Eventually, over many years of exposure to these risks atherosclerotic plaque forms in distinct regions of you arterial tree: the coronary arteries, aorta, iliac and femoral arteries, and carotid arteries. This is what we really mean when we talk about the processes involved in atherogenesis and the development of cardiovascular disease.

As you can plainly see the child-like explanation of high levels of fat and cholesterol sticking to the arteries like mud in a pipe is not only oversimplified but it is a completely inaccurate description of how one develops this extremely complex disease. After learning the facts you might find that defending the high-carb, low fat diet is about as meaningful as promoting a legless man in the Boston Marathon.

HEAL ONE, HEAL MANY

Much of the bane of western civilization has a common origin. The rise of such diseases as the metabolic syndrome and diabetes has led researchers to suggest that they may all share a common inflammatory genesis with atherosclerosis, stroke, and peripheral artery disease. A clue lies in a little known chemical process called the Maillard reaction.

 

[1] NobelPrize.Org Nobel Prize in Physiology or Medicine 1998 (http://www.nobelprize.org/nobel_prizes/medicine/laureates/1998/illpres/) 12/17/2011

[2] Chris Masterjohn High Cholesterol And Heart Disease — Myth or Truth? The Response-to-Injury Rabbit Never Developed Atherosclerosis — Why Not? August 23, 2008
(http://www.cholesterol-and-health.com/Does-Cholesterol-Cause-Heart-Disease-Myth.html)12/14/2011

[original article: Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83(suppl):456S-60S.]

[3] Ricardo J Esper, Endothelial dysfunction: a comprehensive appraisal http://www.cardiab.com/content/5/1/4

[4] (http://www.dietdoctor.com/swedish-expert-committee-low-carb-diet-effective-weight-loss) 06/20/2014

[5] Esper RJ: Interrogando al endotelio. Rev Argent Cardiol 2000, 68:429-439.

[6] Zhu et al. Oxidized LDL, a critical factor in atherogenesis. Cardiovascualr Research. (http://cardiovascres.oxfordjournals.org/content/68/3/353.full#ref-11)12/12/2011.

 

Tags: atherosclerosis, endothelial health, endothelium, Nitric oxide, NO

Category: ENDOTHELIAL DYSFUNCTION, Inflammation, PREVENTIVE MEDICINE