Cardiovascular diseases, atherosclerosis and eicosanoids (good fat vs bad fat)

A cardiovascular disease (CVD) involves heart and blood vessels problems. The most common is the coronary heart disease (CHD), when the coronary arteries become narrow and rigid restricting the blood flow towards the heart. It is also called Ischemic heart disease.

Another common disease is stroke, when the arteries supplying blood to the brain become blocked, reducing the blood flow.

Most of the CVD are related to the atherosclerosis (the build-up of the plaque on the wall of the arteries, gradually obstructing the blood flow due to the narrowing of the arteries). We can also mention here the not-so-common diseases such as heart failure, cardiomyopathy (heart muscle disease), heart valve problems and arrhythmia.

Regarding the cardiovascular diseases, the leading cause of death in the high income countries is CHD, while in the low income countries the infections are the major cause of death. Highest rates of death by CHD are found in Eastern Europe, while the lowest rate is in France and Japan. The substantial increase in Coronary heart disease in Eastern Europe has been linked to tobacco use, dietary behaviors, alcohol use and poor medical care.

Let's talk about atherosclerosis, which is the gradual narrowing of the arteries due to the build of plaque. It is asymptomatic, developing slowly and insidiously. When the oxygen supply cannot meet the demands, because the blood flow is impaired, the problems start to manifest (if it is happening in the heart is ischemia, in the brain is stroke, outside of those two areas is peripheral vascular disease).

The normal artery contains three layers. The inner layer - the endothelium - is in direct contact with the blood. The middle layer contains smooth muscle cells that expands and contracts the blood vessels. The outer layer is composed mostly form connective tissue. The experts believe that the plaque begins to form due to the damaged endothelium, highly supported by an elevated lipids level in the blood, high blood pressure and smoking. Because of the damage, we have white cells sticking to the endothelium, as this layer starts to produce sticky molecules called adhesion molecules, with role in the capture of the white cells. After adhesion, the white cells can move even further into the wall of the arteries. (including t-cells and macrophages). In the vessel wall, the macrophages can take up lipid droplets, becoming foam cells and the wall gradually thicken as it fills up with lipids. When the process advances, the smooth muscles move up to the inner layer and start to produce collagen, giving a connective tissue appearance to the inner wall. As the atherosclerotic process advances even more, cells die and the cell debris and lipids accumulates in the central region of the plaque (called lipid core or necrotic core). Lipids from the atherosclerotic plaque primarily originate from LDL cholesterol, which is interacting with the macrophages creating foam cells, which in turn produce molecules that aggravate the inflammation.

The lipid hypothesis says that lipids, especially LDL cholesterol are deposited in the atherosclerotic lesions and it is a 60 years old supposition. But the idea that elevated lipid levels contribute casually to atherosclerosis is still faced with skepticism. The other mainstream hypothesis is the inflammatory one, stating that inflammation and the immune system got a role in the apparition of the atherosclerosis. It is not proved yet that anti-inflammatory therapy reduces the myocardial infarctions (heart attack).

What we know is that the atherosclerosis lesions are quite stable most of the time, as the lipid core is covered in a thick layer of materials creating the fibrous cap. When inflamed, the white cells produce molecules that gradually break the fibrous cap. The plaque is thinning out and break, then rupture of the plaque leads to thrombosis, triggering the blood clotting. The blood clot can occlude the blood vessel partially or completely at the site of rupture. The blood clot stays there or it is dislodged and block the blood vessel elsewhere. Thrombosis is the formation of a thrombus (blood clot) inside of a blood vessel, impairing the blood flow. Blood clots are formed via coagulation (a process characterized by activation, adhesion and aggregation of the platelets). When someone suffer from heart attack, receiving rapid treatment with thrombolytic drugs (blood clot dissolvants) can save them.

The interesting part is that the blood coagulation is controlled by certain eicosanoids (as we know the eicosanoids are made from unsaturated fatty acids). A way to deal with this is to use not-steroidal anti-inflammatory drugs to inhibit the synthesis if the eicosanoids, blocking the cyclooxigenase enzyme, as primary and secondary prevention (for people who already had a heart attack). Because the eicosanoids are made mostly from essential fatty acids, the types of poli-unsaturated fatty acids present in our diet can influence the production of eicosanoids or just to put it in another way, the fatty acids that we eat may influence the blood clotting, in a good or a bad way. 

And another thing for you to know, the atherosclerosis process can be reversed and reduced using a right diet. We will talk about this another time. 

Eicosanoids, atherosclerosis and cardiovascular diseases

In my next post i will try to delve even further in the role played by the eicosanoids in the prevention of the cardiovascular diseases.

I am working currently at a careful wording, in order to not use to many scientific terms. I try.

Talk to you soon.

The eicosanoids and their relation with the essential fatty acids

This is a bit complicated, but please read slowly and check the connections with the previous posts.

Not very well known, the eicosanoids have roles in virtually every process in the body. Mainly they are binding to receptors on the surface and inside the cells. They can be categorized in prostaglandins (prostacyclins, thromboxanes) and leukotrienes (lipoxins).

The main substrate for eicosanoids synthesis is the arachidonic acid, resulted from the linoleic acid, one of the essential fatty oils. The prostaglandins synthesis from arachidonic acid, catalyzed by cyclo-oxigenase, can be inhibited by certain non-steroidal anti-inflammatory (Aspirine).

The other essential fatty acid - the linolenic acid - is transformed in EPA - a precursor for other eicosanoids synthesis - types that have more anti-inflammatory properties. We can mention Resolvins - which are made only from EPA.

In US and Norway, the main source for linolenic acid is soybean oil and its derivatives (tofu and other soybean-based products). EPA and DHA are obtained from krill and algae, but the real source is the algae producing the EPA/DHA, which is consumed by the krill, which in turn is eaten by the fishes. (30% of the fatty acids are in DHA form). In the infant formula all over the globe, the DHA  is coming from algae.

As you can see, i mentioned the essential fatty acids, the linoleic (part of the n-6 fatty acids family) and the linolenic acid (part of the n-3 fatty acids family). Those fatty acids need to be provided in diet, the lack of it can lead to poor growth and even death. They are essential because mammals cannot introduce double bonds beyond Carbon10 (counting from the carboxyl (end of the fatty acid). We cannot introduce Delta12 and Delta15, but we can make arachidonic acid (C20:4, N-6) from linoleic acid (C18:2:N-6) and EPA (C20:5,N-3) from linolenic acid ( C18:3, N-3).

The linoleic acid is a precursor for the arachidonic acid, source for various eicosanoids (functions in the body, pain management, immune function, blood pressure regulation and blood clotting). The linolenic acid is a precursor for EPA (eicosapentoic acid) and DHA (docosahexapentoic acid), serving to certains prostaglandins, such as the phospholipids in the brain and retina (from DHA). EPA and DHA can be found only in fatty fish and are sometimes reffered as fish oil fatty acids. A vegan or vegetarian diet will never have any EPA/DHA, so you will need to compensate by choosing good sources for linoleic and linolenic acids.