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One of our body's seven defences - Angiogenesis

Angiogenesis is the process by which our blood vessels are formed and maintained in our body.

Angiogenesis is one of the first targets of the SARS-CoV-2 coronavirus, infiltrating our body to attack the connection between the cells that make up our blood, lymph, and other vessels by rupturing them. It is on this basis that clots mainly occur in our body.

Its other purpose is apparently to get into the primary vascular system, the PVS (Primo Vascular System), where microvessels, 19 amino acids and 16 free mononucleotides, etc., circulate. There, SARS-CoV-2 wraps itself with proteins "friendly" to our body and so tricks immune cells into perceiving it to be of normal human origin so they don't attack and destroy it.

Here and now, we will mainly focus on angiogenesis.

Every one of us has cancer cells living and growing in our body. Every one - even you who are reading this.

At autopsy, people who have never had a cancer in their life and have never been diagnosed with one:

- almost 40% of women between the ages of forty and fifty have microscopic tumors in their breasts;

- about 50% of men between fifty and sixty have microscopic cancer in their prostate gland;

- almost 100% of people over the age of seventy have microscopic tumors in their thyroid. {J. Folkman and R. Kalluri, "Cancer without Disease" Nature 427, no. 6977 (2004): 787.}

Such tumors develop in our bodies when healthy cells make natural errors in cell division or when cellular DNA mutates as a result of environmental factors. Up to ten thousand errors occur in the DNA of dividing cells in your body every day, making the onset of cancer not only common but inevitable. { B. N. Ames, M. K. Shigenaga, and T. M. Hagen, "Oxidants, Antioxidants, and the Degenerative Diseases of Aging," Proceedings of the National Academy of Sciences USA 90, no. 17 (1993): 7915-7922; S. Clancy, "DNA Damage and Repair.

Yet these microscopic malignant tumors are completely harmless. Most of them will never become dangerous. They are small at first - smaller than the ball at the tip of a ballpoint pen, and as long as they do not grow and penetrate organs, they cannot spread and kill.

Your body has a remarkable defense system that keeps microscopic cancer small, leaving it to starve without the blood supply and nutrients it needs, and you can improve the activity of this defense system through the food you eat. Over a hundred foods can amplify your body's ability to not feed the tumor cells and keep the growth small and harmless. These foods include soy, tomatoes, black raspberries, pomegranates and even some surprising ones like licorice, beer and cheese. The defensive arsenal you need to keep these tumors in check can be found at the grocery store, market or in your garden.

The defense system that prevents our body from intercepting cancer in this way is called angiogenesis. Angiogenesis is the process by which the body forms and maintains blood vessels. Under normal circumstances, blood vessels sustain life by delivering oxygen and vital nutrients to all organs. But when an abnormal amount of blood vessels grow, they begin to nourish microscopic tumors. Proper angiogenesis regulates when and where blood vessels should grow and can prevent tumors from creating their own blood supply to supply the oxygen they need to grow. When the body loses its ability to control blood vessels, a wide range of diseases can occur, including cancer.

As long as angiogenesis is functioning well, blood vessels grow in the right place at the right time - neither too many nor too few, but in the right amount. Maintaining this perfect balance in the circulatory system is the underlying mechanism by which angiogenesis protects our health by keeping us in a state called homeostasis. Homeostasis is the maintenance of stability in the body to function normally by adapting to constantly changing conditions. Angiogenesis plays a vital role by creating and maintaining the entire circulatory system while adapting it to changes over the course of our lives to protect our health.

Thanks to this powerful protective defense system, which naturally reduces the blood supply to tumors, cancer does not develop. {J. Folkman and R. Kalluri, "Cancer without Disease," Nature 427, no. 6977 (2004): 787}

Later, we'll tell you how the latest knowledge about angiogenesis is shaping our understanding of what foods can help the angiogenesis system maintain homeostasis and what to eat to starve cancer, strengthen the vessels that supply blood to your heart, and fight off deadly diseases so you can live longer and be healthier. But, to fully appreciate how food affects angiogenesis and your health, we'll soon take a look at how your blood vessels work for you day by day.

How does angiogenesis work?

There are ninety-six thousand miles of blood vessels inside you whose job it is to deliver oxygen and nutrients to keep cells alive. These are the life-giving vessels that nourish our healthy organs and protect us from disease. If your vessels were connected lengthwise, they would circle the globe twice. Remarkably, it only takes sixty seconds from the moment your heart pumps a drop of blood for it to pass through the body and back out again.

The smallest blood vessels are called capillaries. They are thinner than a hair and your body has 19 billion of them. Capillaries have a unique relationship with all other cells because they are the last link in the circulatory system chain that blood supplies to your cells. Because they are at the end of the chain, literally every cell in the body is located among two hundred micrometers of capillaries. {M. Lovett, K. Lee, A. Edwards, and D. L. Kaplan, "Vascularization Strategies for Tissue Engineering," Tissue Engineering Part B: Reviews 15, no. 3 (2009): 353-370.}

That's a really high density. The capillaries of each organ have specific densities and arrangements, depending on how the organs work and what blood flow they need. Your muscles, for example, need a lot of oxygen, so they need four times as much blood supply as your bones, which have a structural-support function. Other organs requiring a good blood supply are the brain, heart, kidneys and liver. The capillary density of each of these organs is an incredible three thousand blood vessels per cubic millimeter, which is thirty times more than bones.

Viewed microscopically, capillaries look like a work of art sculpted to fit the organ from which they grow.

The ones that nourish your skin look like rows of Velcro hooks - loop after loop, they provide the blood that gives your skin its warmth and color.

The capillaries along your nerves - from your spinal cord to your fingertips - resemble telephone wires, feeding your neurons and keeping your senses sharp.

The capillaries in your colon are arranged in beautiful geometric shapes like honeycombs to allow them to expand as the intestine fills with digested food, while at the same time providing it with the maximum surface area needed to reabsorb fluids into the bloodstream.

Angiogenesis is so fundamental to the maintenance of life that it begins in the reproductive system even before conception. When the sperm reaches the egg, the uterine lining (endometrium) is already prepared with an increased number of new blood vessels ready to receive and nourish the fertilized egg. If pregnancy does not occur, this layer is shed with menstruation each month. If the fertilized egg implants, the blood vessels act as the first line of supply for the developing fetus. About eight days after implantation, a new vascular organ, the placenta, is created to supply blood from the mother to the fetus. {Robyn D. Pereira et al. "Angiogenesis in the Placenta.

Over the next nine months, an angiogenic symphony occurs in the fetus - the entire circulatory system is formed from scratch and then every single organ is built in the developing body. Toward the end of pregnancy, as the body prepares for birth, the placenta relies on a natural angiogenic factor called sFlt-1, which slows the building of blood vessels. This ability to Turn On, Slow Down, and Turn Off is the hallmark of the angiogenesis defense system, not only in building life during pregnancy, but also in protecting health during life.

Angiogenesis defense is a method of defense in all animals with blood circulation, including humans. When you've had a deep cut, whether from surgery or injury, you've surely seen the site begin to change within seconds, starting a process that lasts until the wound heals.If you've ever skinned your knee to the point of bleeding and then a crust formed over the wound, if you split that crust too soon, this process unfolds before your eyes.The tissue under the rind is bright red.Thousands of new blood vessels grow here, whose job it is to heal the site.When you look at these processes, you see angiogenesis that starts in the injured tissue as soon as the bleeding starts.The start is given by hypoxia - the lower oxygen levels due to the interruption of normal blood flow in the wound.A lack of oxygen is a signal for most blood vessels to grow to deliver more oxygen.Hypoxia causes injured cells to start sending protein signals called growth factors to stimulate angiogenesis.Inflammation is very important at the beginning of the healing process.Inflammatory cells called macrophages and neutrophils flock to the wound to clear any bacteria and debris from the wound and secrete their own angiogenic growth factors that stimulate the process of blood vessel formation.From this point, several events begin to take place at the cellular level in order for blood vessels to grow.Thanks to a special kind of cells lining the inner surface of the veins - endothelial cells - the rescue squad awaits the signaling growth factors that instruct the endothelial cells to unfold.Approximately one trillion endothelial cells form the layer covering the inner surface of the walls of your circulatory system.This makes them one of the most numerous types of cells in your body.Think of each of these endothelial cells as a car engine connected to the ignition switch.Now imagine the growth factors secreted from the injury site like car keys.Growth factors fit specific receptors, probing the surface of endothelial cells, like car keys fit the ignition key.When the right key goes into the right lock, the engine starts and the endothelial cells are ready to begin migrating to the source secreting protein growth factors and start dividing and forming tubes that will become new blood vessels.First, however, the endothelial cells need to exit the vein.They secrete enzymes that break down the tubular wall of the vein, piercing it.From this point on, activated endothelial cells begin to sprout through these openings, following the gradient of growth factors sent from the injured site and forming new blood vessels in that direction.The newly formed blood vessels elongate and join at their tips to form capillary loops.The more capillary loops form in the injured area, the more new blood circulation pathways are built.

Newly formed blood vessels are too fragile to maintain blood flow on their own, so they are assisted by another type of cell, pericyte cells, which help them mature.Pericyte cells help in two or three ways.The first is by wrapping around the endothelial tubes like a sock around an ankle to give them structural strength.At the same time, pericytic cells slow down angiogenesis so that there is no excess of blood vessels.{L.A. DiPietro, “Angiogenesis and Wound Repair: When Enough Is Enough,” Journal of Leukocyte Biology 100, no.5 (2016): 979-984.}Pericytic cells change shape.Once anchored in a new blood vessel, they extend tentacles to engulf the endothelial cells around them.A single pericyte can touch twenty cells at once and release a chemical signal that stops angiogenesis in surrounding cells.{A.Orlidge and P. A. DAmore, "Inhibition of Capillary Endothelial Cell Growth by Pericytes and Smooth Muscle Cells", Journal of Cell Biology 105, no.3 (1987): 1455-1462.}As the new vessels grow and stabilize, blood begins to flow through them.The new influx of oxygen reduces the sending of signaling growth factors, which slows and eventually stops angiogenesis.At the same time, natural inhibitors of angiogenesis are released in the area, which further suppress vessel formation.Once the new blood vessels are stabilized, the inner layer of endothelial cells secretes proteins called survival factors that help heal the site with angiogenesis.When built well, the new protective blood vessels can last a lifetime, keeping the skin and other organs alive.The protective angiogenic system constantly senses where and when more vessels are needed to maintain organ health and function.Like master masons, blood vessels sense that your muscles need increased blood flow after a workout.At the same time, the system is constantly alert for situations in which blood vessels need to be tightened.Not too little, not too much, but just as much as is needed to maintain balance - this is the twenty-four hour function of the angiogenesis defense system.We seem to have a dimmer here.When necessary, the intensity is increased to grow more blood vessels.When angiogenesis needs to be reduced, the body has endogenous (naturally occurring in the body) inhibitors of angiogenesis that limit the process.Stimulators and antagonists are everywhere - including in our muscles, blood, heart, brain, breast milk and even semen.Your body must have perfect control over angiogenesis to maintain optimal health.Over the course of life, however, many factors can compromise this protective system, and either there is excessive vascularization that nourishes diseased tissue, or the other option is insufficient vascularization, which can lead to tissue loss and death.In the following posts, you will learn about foods that help protect the angiogenesis system to help our body resist disease.But first let's go back to the microscopic cancers/that grow in your body to see how defenses are broken down and what the dire consequences are.So you will learn why it is so important to eat exactly that food that strengthens your health.The main reason microscopic cancers don't grow is your body's natural inhibitors of angiogenesis.These countermeasures keep tumors under control by cutting off their blood supply.As early as 1974, researchers at Harvard Medical School discovered that until blood vessels grow to feed tumors, cancer cells remain dormant and harmless.Your immune system, which we'll tell you about later, eventually identifies these cancer cells and destroys them.Over time, however, some small foci of cancer cells can overwhelm the defense system and neutralize angiogenic inhibitors by secreting massive amounts of the same signaling growth factors that are involved in wound healing.In laboratory experiments, it has been found that after a small group of cancer cells grow new blood vessels, the tumor can grow exponentially, increasing in size sixteen thousand times in just two weeks after the initiation of angiogenesis.{A.Orlidge and P. A. DAmore, "Inhibition of Capillary Endothelial Cell Growth by Pericytes and Smooth Muscle Cells", Journal of Cell Biology 105, no.3 (1987): 1455-1462.}

When tumors recruit the defensive angiogenesis system to develop their own circulation, a harmless cancer very quickly turns into a potentially deadly one.Even worse, the same blood vessels that feed the cancerous tumors become exit channels through which the malignant cells enter the blood and edema.This is known as metastasis and is the most dangerous aspect of cancer.Patients rarely die from their original tumor, which can often be surgically removed, it is the metastases that eat away at the body and cause death.By helping the body prevent unwanted angiogenesis, we can do a lot in the fight against cancer.The goal is to boost your angiogenesis protection, helping the body's natural defenses to keep the blood vessels in balance - that is, to keep cancer cells from feeding and growing.The first patient to be successfully administered angiogenic therapy was 12-year-old Tom Briggs of Denver, Colorado.He was diagnosed with pulmonary capillary hemangiomatosis - tumors growing in his lungs.As the tumors grew, the boy's breathing became difficult and he could not practice his favorite sports like basketball, and sometimes he could not even sleep at night.As a last desperate measure, they gave Tom a drug called interferon alpha, which doctors know could stop angiogenesis.Within a year, the tumors in the boy's lungs had shrunk and Tom was back to living the life of a normal kid.Tom's case is so remarkable that it was published as the "first human trial" in the New England Journal of Medicine - a glimpse into the future of tumor treatment.{C.W. White et al., “Treatment of Pulmonary Hemangiomatosis with Recombinant Interferon Alfa-2a”, New England Journal of Medicine 320, no.18 (1989): 1197-1200.}Biotechnology companies began developing angiogenic targeting drugs to treat tumors in the 1990s.The first case of cancer in which a response to angiogenesis therapy was observed was colon cancer.Avastin targets the tumor's blood vessels and improves patient survival.Many other cancers have become curable by boosting the body's own anti-angiogenesis measures—something that has been achieved with Avastin and more than a dozen other designer drugs that inhibit angiogenesis.The types of cancer are kidney, lung, brain, thyroid, liver, cervical, ovarian and breast, as well as multiple myeloma.In 2004, US Food and Drug Commissioner Mark McClellan stated: "Angiogenesis inhibitors can now be considered the fourth option for cancer treatment (after surgery, chemotherapy, and radiation therapy).{Y.Cao and R. Langer, “A Review of Judah Folkman's Remarkable Achievements in Biomedicine,” Proceedings of the National Academy of Sciences USA 105, no.36 (2008): 13203-13205.}Excessive angiogenesis drives the development of many other diseases besides cancer - such as vision loss.When the eyes are healthy, we see because light passes through a crystal clear fluid to the retina and is registered by the brain without the intervention of blood vessels.In the eye, angiogenesis is so tightly controlled that the endothelial cells that line the inside of the blood vessel wall in the retina divide only twice in a person's lifetime.However, in age-related macular degeneration, which is the leading cause of blindness worldwide in people over the age of sixty-five, as well as in diabetic vision loss, there is neovascularization of the eye tissues and leakage and hemorrhages.These dire consequences of unwanted vascularization impair vision.Fortunately, today these conditions can be treated with AKHL-approved biologic drugs that are injected into the eye by an ophthalmologist to stop destructive vascularization and protect vision.Some patients even manage to recover their lost vision.I had a patient who was blind as a result of macular degeneration and could not drive or play golf, once her favorite pastimes.After treatment, she started driving again and continued to work on her backswing on the golf course.In rheumatoid arthritis, as in osteoarthritis, inflammation in the joints leads to neovascularization and secretion of destructive enzymes.These enzymes break down cartilage, which causes debilitating joint pain.In psoriasis, a threatening skin disease, pathological angiogenesis under the skin leads to the formation of red spots, which are accompanied by swelling, irritating itching and pain.It has been established that massive and pathological vascularization is also observed in Alzheimer's disease.In 2003, an article published by psychiatrist Anthony Vanucci in The Lancet suggested that these abnormalities in blood vessels in the brain contribute to Alzheimer's disease.{A.H. Vagnuccijr.and W. W. Li, “Alzheimer's Disease and Angiogenesis,” Lancet 361, no.9357 (2003): 605-608.}We now know that the blood vessels in the Alzheimer's brain are abnormal and do not actually improve blood flow to the brain, but instead secrete neurotoxins that kill brain cells.Even obesity is strongly associated with angiogenesis.Although obesity is a multifactorial disease, overeating and eating the wrong foods greatly increase the levels of angiogenesis-stimulating growth factors that circulate in the blood.{J.V. Silha, M. Krsek, P. Sucharda, and L. J. Murphy, “Angiogenic Factors Are Elevated in Overweight and Obese Individuals,” International Journal of Obesity 29, no.11 (2005): 1308-14.}Like tumors, fat tissue needs new blood vessels to grow and feed fat cells.{M.A. Rupnick et al., "Adipose Tissue Mass Can Be Regulated through the Vasculature", Proceedings of the National Academy of Sciences USA 99, no.16 (2002): 10730-10735.}For all of these health problems, and many others, modern antiangiogenic drug therapies have shown promising results in laboratory studies and clinical trials.Spaying the swollen blood vessels is important, but equally important is maintaining the body's ability to develop an adequate circulatory system to protect organs that need to increase or restore their blood supply.As we age, our circulatory system often weakens, so it needs to be strengthened to nourish and keep tissues and organs healthy.Failure to mount a protective angiogenic response has severe consequences.One such consequence is neuropathy.Neuropathies occur when nerve function is impaired.In these cases, stiffness or pain may occur, ranging from mild to debilitating.Your peripheral nerves are your electrical wiring that runs throughout your body, relying on commands from your brain to your muscles that tell them to contract or relax.Nerves also carry sensations from the skin and muscles back to the brain.These electrical cords have their own mini blood supply, called the vasa nervorum, which maintains blood supply to the nerves.When the vasa nervorum collapses, the nerves begin to die.Symptoms range from numbness to excruciating pain or complete immobility in the arms, legs and feet.In people with diabetes, the blood supply to the nerves can be damaged, especially if they do not maintain good blood sugar control.Diabetes also slows down angiogenesis, which leads to nerve damage.Scientists are working on new ways to improve blood flow to nerves through therapeutic angiogenesis.In laboratory studies of diabetic animals, a gene for the angiogenic protein VEGF (vascular endothelial growth factor) was injected into muscle and found to increase blood flow to nerves and restore nerve function to levels close tothe normal ones.{P.Schratzberger et al., “Reversal of Experimental Diabetic Neuropathy by VEGF Gene Transfer”, Journal of Clinical Investigation 107, no.9 (2001): 1083-1092.}Another common cause of peripheral neuropathy is the administration of chemotherapy, which, in addition to killing cancer cells, can also be highly toxic to nerves and destroy their mini circulatory system.In a laboratory study, gene therapy using VEGF completely protected nerves and their blood supply, so they did not lose their function.{R.Kirchmair et al., “Therapeutic Angiogenesis Inhibits or Rescues Chemotherapy-Induced Peripheral Neuropathy: Taxol- and Thalidomide-Induced Injury of Vasa Nervorum Is Ameliorated by VEGF”, Molecular Therapy 15, no.1 (2007): 69-75.}

If you have a chronic wound, one of your doctor's primary goals should be to stimulate angiogenesis to improve blood flow and speed healing. This can be done through various medical devices and other techniques, including through food.In the future, we will look at which foods stimulate angiogenesis.Your heart and brain also rely on the angiogenic defense system to respond whenever there is a threat to their own circulation.Rapid restoration of blood flow to these organs is literally life or death.When there are blockages in the blood vessels, which happens with atherosclerosis, your defense system shifts into high gear and new blood vessels begin to form to build a natural bypass around the blocked channels.Natural bypasses, called collateral vessels, occur when blockages slowly form, starting with narrowing of the coronary vessels or carotid arteries.People can live years or decades with coronary heart disease if their protective angiogenic system is doing its job.Even in the case of sudden blockages such as heart attack or ischemic stroke, if the patient survives, the protective mechanism of angiogenesis is triggered to form natural bypasses.This protection kicks in slowly if the patient has a disease that inhibits angiogenesis, such as diabetes or hypercholesterolemia, or if the patient is a smoker or very old.Clinical trials of new angiogenic therapies that stimulate angiogenesis in the heart or brain are underway, but they are still in the experimental phase and will be years before they can be used to treat patients.If pharmaceutical companies used information medicine, they would sift through the side effects and contraindications for each individual product much faster and qualitatively.This would lead to the clearing of these adverse effects of all types of medication.In part two, I'll tell you about foods you can use at home to stimulate cardiovascular angiogenesis and healing.Foods and angiogenesisIt is clear that a fully functioning angiogenic defense system protects us from many diseases.Your health depends on your circulatory system being in balance - the blood vessels in your organs should be neither bulging nor in short supply.When this balance is disturbed, the body needs help.Scientists at biopharmaceutical and medical device companies are racing to develop new treatments, but that could take a decade or more, cost more than $1 billion, and even if successful, may not be available to everyone.who needs it, because of its price or availability.After all, these drugs and methods are designed to treat diseases, not to prevent them.Your diet can serve to prevent disease in addition to helping to treat it.Research conducted around the world reveals that specific foods and beverages, many of which we know well and love, can stimulate angiogenesis protection, whichever way you want to tip the scales.Even how you cook and combine food ingredients can affect angiogenesis.This opens up a whole new perspective to the way we look at the food we eat and the way we eat it.It also opens new doors if you want to increase your chances of preventing diseases influenced by angiogenesis.If you're currently struggling with an angiogenesis-dependent condition, choosing the right foods can help you manage and even beat the disease.Evidence for the power of this approach is mounting.Asians who consume a lot of soy, vegetables and tea have a significantly lower risk of developing breast cancer and other cancers.There are more than sixty-nine thousand people over the age of 100 in Japan. {Emiko Jozuka and Yoko Ishitani, “Worlds Oldest Person Dies at 117,” CNN,}In China, the population of centenarians is also increasing.My great-uncle, who lived to be 104 years old, lived in the city of Changshu, near Shanghai, at the foot of Yushan Mountain, where green tea grows.The centenarians from the Greek island of Ikaria and from central Sardinia eat a Mediterranean diet that is full of angiogenesis-stimulating ingredients and is not strictly vegan.Understanding that angiogenesis is one of the crucial defense systems is the key to the secrets of long-term health and wellness.

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