Atherosclerosis: hardening of the arteries

Posted on July 23rd, 2018

Atherosclerosis is a condition affecting the arteries, which are responsible for carrying oxygen-rich blood from your heart to your body. Atherosclerosis involves the buildup of fats, cholesterol, and other substances on the artery walls. The buildup is called plaque, and it can restrict blood flow in the body.

Reduced blood flow through your arteries means less oxygen supplied to the organs and tissue throughout the body, which impacts how well they function. Plaque that builds up in the arteries may also burst and result in a blood clot.

Buildup of plaque in the arteries can occur anywhere in the body, and it can lead to many other health conditions, such as heart attack, stroke, coronary heart disease, peripheral artery disease, or chronic kidney disease.

Causes

Atherosclerosis is a progressive disease that may begin as early as childhood and impacts different people at different ages. While the exact cause is not known, studies suggest that plaque buildup begins when the inner lining of the arteries is damaged by one of several factors, including smoking, high cholesterol, high blood pressure, or high blood sugar.

Symptoms and Diagnosis

Because atherosclerosis develops gradually over time, most patients will not experience any symptoms in the early stages of the disease. Symptoms typically begin when an artery has narrowed so much that not enough blood gets to your organs and tissues.

When symptoms do occur, they will vary based on the location of the narrowed arteries. Symptoms may include chest pain, numbness or weakness in arms or legs, slurred speech, temporary loss of vision in one eye, leg pain when walking, high blood pressure, or kidney failure.

If you experience any symptoms that could be related to atherosclerosis, see your doctor as soon as possible. There are many diagnostic tests your doctor may run to look for signs of atherosclerosis, including blood tests, electrocardiogram (EKG), chest x-ray, echocardiogram, CT scan, a stress test, or an angiogram. They may also run an ankle brachial index, which measures the blood pressure in your arm compared to the blood pressure in your ankle to determine how well blood is flowing through your arteries.

Treatment

As with many other heart conditions, treatment for atherosclerosis may include a combination of lifestyle changes, medications, and procedures.

Recommended lifestyle changes to both prevent and treat atherosclerosis include eating a heart-healthy diet, getting regular exercise, quitting smoking, losing weight, and reducing stress. Medications may include any of the following:

• Cholesterol drugs to lower LDL cholesterol

• Anti-platelet medications to reduce the chances of platelets clumping in the arteries to form a clot

• Beta blockers to reduce heart rate and blood pressure

• ACE inhibitors to lower blood pressure and reduce the risk of heart attack

• Calcium channel blockers to lower blood pressure

• Diuretics (water pills) to lower blood pressure

• Other medications to control contributing factors or symptoms, such as diabetes, inflammation, or leg pain

In cases of severe atherosclerosis, a medical procedure may be required. Options include a coronary angioplasty to open narrowed arteries and placement of a stent to keep them open, coronary artery bypass grafting to go around the narrowed arteries, or an endarterectomy to surgically remove plaque from the arteries.

If you have a family history of atherosclerosis, are a smoker, have high blood pressure, or have high cholesterol, contact the Oklahoma Heart Hospital today to schedule an appointment to discuss your risk factors for atherosclerosis.

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Cause of hardening of the arteries – and potential treatment – identified

A team of UK scientists have identified the mechanism behind hardening of the arteries, and shown in animal studies that a generic medication normally used to treat acne could be an effective treatment for the condition.

Artery hardening happens to everyone as they age…but up until now we haven’t known what controls this process and therefore how to treat it

Melinda Duer

The team, led by the University of Cambridge and King’s College London, found that a molecule once thought only to exist inside cells for the purpose of repairing DNA is also responsible for hardening of the arteries, which is associated with dementia, heart disease, high blood pressure and stroke.

There is no current treatment for hardening of the arteries, which is caused by build-up of bone-like calcium deposits, stiffening the arteries and restricting blood flow to organs and tissues.

Supported by funding from the British Heart Foundation, the researchers found that poly(ADP ribose), or PAR, a molecule normally associated with DNA repair, also drives the bone-like calcification of arteries.

Additionally, using rats with chronic kidney disease, the researchers found that minocycline – a widely-prescribed antibiotic often used to treat acne – could treat hardening of the arteries by preventing the build-up of calcium in the circulatory system. The study, the result of more than a decade of fundamental research, is published in the journal Cell Reports.

“Artery hardening happens to everyone as they age, and is accelerated in patients on dialysis, where even children develop calcified arteries. But up until now we haven’t known what controls this process and therefore how to treat it,” said Professor Melinda Duer from Cambridge’s Department of Chemistry, who co-led the research as part of a long-term collaboration with Professor Cathy Shanahan from King’s College London.

“This hardening, or biomineralisation, is essential for the production of bone, but in arteries it underlies a lot of cardiovascular disease and other diseases associated with ageing like dementia,” said Shanahan. “We wanted to find out what triggers the formation of calcium phosphate crystals, and why it seems to be concentrated around the collagen and elastin which makes up much of the artery wall.”

In earlier research, Duer and Shanahan had shown that PAR – normally associated with the repair of DNA inside the cell – can in fact exist outside the cell and is the engine of bone production. This led the researchers to hypothesise that PAR may also play a role in biomineralisation. In addition, PARP1 and PARP2, the dominant PAR-producing enzymes, are expressed in response to DNA damage and oxidative stress, processes which are associated with both bone and vascular calcification.

“We could see signals from bone that we couldn’t explain, so we looked for molecules from first principles to figure it out,” said Duer.

“I’d been thinking for years that hardening of the arteries was linked to DNA damage, and that DNA damage is a pathway switched on by many agents including smoking and lipids,” said Shanahan. “When this pathway is switched on, it drives the pathologies associated with ageing. If enough damage is present, the arteries will eventually reflect it.”

Using NMR spectroscopy, the researchers found that when the cells become stressed and die, they release PAR, which binds very strongly to calcium ions. Once released, the PAR starts mopping up calcium into larger droplets which stick onto the components in artery walls that give the artery its elasticity, where they form ordered crystals and solidify, hardening the arteries.

“We never would have predicted that it was caused by PAR,” said Duer. “It was initially an accidental discovery, but we followed it up – and it’s led to a potential therapy.”

Having discovered the links between DNA damage, PAR, bone and artery calcification, the researchers then looked into a way of blocking this pathway through the use of a PARP inhibitor.

“We had to find an existing molecule that is cheap and safe, otherwise, it would be decades before we would get a treatment,” said Shanahan. “If something has already been shown to be safe in humans, the journey to the clinic can be much faster.”

Working together with Cycle Pharmaceuticals, a Cambridge-based company, the researchers identified six known molecules that they thought might inhibit the PARP enzymes. Detailed experiments with these showed that the antibiotic minocycline was highly effective in preventing hardening of the arteries.

“It’s been 12 years of basic research to get to this point,” said Duer. “We set out with absolutely no expectation of finding a potential treatment – there is no treatment currently and nobody would have believed us if we had said at that point we were going to cure hardening of the arteries.”

The technology has been patented and has been licensed to Cycle Pharmaceuticals by Cambridge Enterprise, the University’s commercialisation arm. The researchers are hoping to carry out a proof of principle trial in patients in the next 12 to 18 months.

“Blood vessel calcification is a well-known risk factor for several heart and circulatory diseases, and can lead to high blood pressure and ultimately, a life-threatening heart attack,” said Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation. “Now, researchers have shown how calcification of the walls of blood vessels takes place, and how the process differs from normal bone formation. By doing so, they have been able to identify a potential treatment to reduce blood vessel calcification without any adverse effects on bone. This type of treatment would benefit many people, and we eagerly await the results of the anticipated clinical trials looking at whether this drug lives up to its early promise.”

Reference:
Karin H. Müller et al. ‘Poly(ADP ribose) links the DNA damage response and biomineralization. ’ Cell Reports (2019). DOI: 10.1016/j.celrep.2019.05.038

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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11 Jun 2019

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False colour image of calcium phosphate deposits on bone

Credit: Melinda Duer

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causes, symptoms, diagnosis and treatment in Moscow

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Aortic sclerosis is a chronic pathology of the arterial system, which is characterized by thickening of the aorta due to impaired cholesterol metabolism in the body. The presence of atherosclerotic changes in the walls of blood vessels is most often detected in the elderly, mainly in males. Aortic sclerosis (or, as the disease is also colloquially called – heart sclerosis) is considered the most frequent and dangerous localization of the pathological process. As a rule, cholesterol plaques are located on separate parts of the aorta, but in difficult cases they can affect the entire inner surface of the blood vessel. Due to the weakening of blood flow to the heart, coronary insufficiency develops, which can be fatal. Cardiologists at the Yusupov Hospital prescribe complex treatment if a patient has aortic sclerosis, aimed at compensating for cardiac activity, normalizing lipid metabolism, and preventing serious complications.

Aortic sclerosis: etiology and pathogenesis

The development of pathology can be triggered by the following factors:

• malnutrition;
• chronic infectious diseases – tuberculosis, syphilis, etc.;
• endocrine diseases – diabetes mellitus, obesity;
• stress and high levels of adrenaline in the blood;
• hypertension;
• autoimmune diseases;
• smoking and alcohol abuse;
• gout;
• sedentary lifestyle – hypodynamia;
• lack of physical activity;
• hereditary predisposition.

Relief of the patient’s condition is achieved by eliminating provoking factors or reducing their impact.

The pathogenesis of aortic sclerosis consists of two main mechanisms: vascular-platelet and dyslipidemic. In the place of accumulation of platelets (on damage to the vessel wall), the formation of microthrombi occurs. Due to a violation of lipid metabolism, hypercholesterolemia develops. On the vascular walls, there is an accumulation of fats fastened with connective tissue fibers, thus the formation of atherosclerotic plaques occurs, as they grow, the lumen of the vessels is deformed and narrowed. Sclerosis of the aorta of the heart leads to disruption of its blood supply and the development of dysfunction.

Cardiac aortic sclerosis: clinical picture

Symptoms of cardiac aortic sclerosis may differ in accordance with the general condition of the vessels and the location of the pathological focus. The pathology is characterized by a long, asymptomatic course. The first signs of aortic sclerosis can be detected in old age, due to significant pathological changes, wear of the vessel walls. Anxiety in patients is caused by the sudden appearance of severe chest pain, increased pressure, shortness of breath, dizziness. The patient’s health deteriorates sharply, shortness of breath, pain in the chest, abdomen, dyspepsia develops.

A patient suffering from aortic sclerosis has a change in appearance: he looks older than his years, turns gray or bald early, his eyes become dull, skin tone worsens (a large number of folds and small angiomas are noted on it), trophic disorders appear on the lower extremities .

Damage to the thoracic aorta is accompanied by periodic burning pain in the chest, hoarseness or hoarseness of the voice, dysphagia, arterial hypertension, convulsive syndrome, the appearance of early signs of aging and pre-syncope.

Damage to the abdominal part of the aorta is characterized by the occurrence of pressing, unexpressed pain in the epigastrium, constipation, diarrhea, bloating, weight loss, numbness of the legs, swelling of the legs, dystrophic processes (including gangrene), dystonia of the gastrocnemius muscles, erectile dysfunction in men.

Neurologists at the Yusupov hospital, if patients have signs that may indicate aortic sclerosis, quickly conduct a comprehensive diagnosis with an assessment of the state of the heart, vascular system, lipid profile, coagulation activity, after which they prescribe an individual treatment program.

Aortic sclerosis: treatment of pathology

Conservative therapy of aortic sclerosis involves long-term (and often lifelong) administration of drugs that help normalize the metabolism of fats in the body: bile acid sequesters, statins, fibrates, lipid-lowering drugs, polyunsaturated fatty acids, choleretic drugs, vitamins and minerals (C, B2, B6, PP).

Surgical treatment of aortic sclerosis is the removal of an atherosclerotic plaque or thrombus, followed by aortic replacement, which restores normal blood flow. The operation is urgently needed for stroke, renal failure, renal ischemia, because. due to arterial thrombosis, necrosis and peritonitis may develop.

The Yusupov Hospital in Moscow diagnoses and successfully treats pathologies of the cardiovascular system, including sclerosis of the aorta of the heart. The equipment of the clinic allows the doctor to identify the disease with high accuracy and prescribe timely treatment, which prevents the development of dangerous complications. Correction of pathologies is carried out using the latest technologies, for the use of which the Yusupov Hospital has all the necessary modern equipment. The medical coordinator will answer all your questions by phone.

Diseases of the aorta and great vessels

The aorta is the largest artery in the body, originating from the left ventricle of the heart. The maximum diameter of the aorta is normally about 3 cm. Oxygen-enriched arterial blood flows through the aorta and its branches, supplying organs and tissues with oxygen and nutrients. The aorta has several divisions: the ascending aorta, the aortic arch, and the descending aorta.

Aortic surgery is rightfully considered one of the most difficult sections of cardiac surgery, which is carried out in Russia by a few clinics and specialists. In the Federal State Budgetary Institution “FTSSSH them. S.G. Sukhanov” of the Ministry of Health of Russia (Perm) all types of surgical treatment of aortic pathology .

Aortic aneurysm is a ticking time bomb. An aortic aneurysm is a protrusion of the wall due to its thinning or stretching. As a result, a so-called aneurysmal sac appears, which can compress nearby organs and tissues. You can live with it for years, go about your daily activities and not experience any symptoms. Meanwhile, the aneurysm will grow imperceptibly, threatening to rupture at any moment.

Diagnosis of aortic aneurysms

Aortic aneurysms are often discovered by chance, during ultrasound or X-ray examination. If it is detected, urgent treatment is required, since the rupture of the aneurysm leads to hemorrhage, which can lead to death. At the moment of aneurysm rupture, a person feels pain, and his blood pressure begins to drop rapidly due to a large loss of blood.

The most accurate information about the presence of aneurysms is provided by such diagnostic methods as computed tomography, magnetic resonance imaging, and angiography.

Treatment of aortic aneurysms consists in their surgical excision followed by replacement of the removed aortic area with a vascular synthetic prosthesis (tube).

In the Federal State Budgetary Institution “FTSSSH them. S.G. Sukhanov» of the Ministry of Health of Russia (Perm), operations are performed for aneurysms of the ascending aorta and aortic arch, aneurysms of the aortic arch, aneurysms of the descending thoracic aorta, aneurysms of the abdominal aorta, aneurysms of the thoracoabdominal aorta. Aortic root reconstruction technologies are successfully used – valve-preserving operations on the aortic valve – David’s operation. The Center performs operations to reconstruct the aortic arch using various modern methods of brain protection – antegrade cerebral perfusion, circulatory arrest.

Specialists of the Federal State Budgetary Institution “FTSSSH them. S.G. Sukhanov” of the Ministry of Health of Russia (Perm) use endovascular technologies in the treatment of aortic aneurysms. Such operations are carried out in special X-ray operating rooms, their main difference from “big” surgery is the low traumatic nature of the procedure and the rapid recovery of the patient. Through a small puncture on the thigh above and below the enlarged area of ​​the aorta, a stent graft is installed – a scaffold tube that will perform the function of the aorta with complete restoration of blood flow and isolation of the aneurysm.

Abdominal aortic stent graft implantation

• S.G. Sukhanov” of the Ministry of Health of Russia (Perm) provides 90,063 emergency cardiac surgical care to 90,064 patients with a formidable complication of aortic disease – acute dissection.

Aortic dissection is a life-threatening condition resulting from the infiltration of blood into the aortic wall through a tear in its inner lining. In this condition, the aortic wall is divided into layers (stratified), which leads to a number of serious consequences, up to the death of the patient. Aortic dissection is quite often combined with aortic aneurysms and has some features similar to them, in particular, the fragility of the aortic wall. Mortality with it is up to 90% within a month, and half of the patients die in the first hours from aortic rupture and cardiac tamponade (compression of the heart with blood in the pericardial sac).

Aortic dissection can start for no apparent reason, but it often occurs as a result of heavy physical work or due to a sharp rise in blood pressure. In most cases, at the time of dissection, pain of varying intensity occurs, ranging from unpleasant pain in the area of ​​dissection to very severe pain. Sometimes the pain can cause pain shock in combination with a sharp decrease in blood pressure and subsequent fainting.

Diagnosis of aortic dissection

It is far from always possible to suspect the onset of aortic dissection in a timely manner. Due to the fact that aortic dissection can “mask” as other diseases, it is often mistaken for acute myocardial infarction, acute cerebrovascular accident or the so-called “acute abdomen”. In such a situation, it is extremely important to exclude acute myocardial infarction, since the treatment of aortic dissection and myocardial infarction involves diametrically opposed measures.

For the diagnosis of aortic dissection, research methods such as electrocardiography (ECG), radiography, ultrasound (echocardiography – EchoCG, in particular transesophageal, abdominal ultrasound), magnetic resonance imaging, computed tomography with intravenous contrast agent are used. Angiography of the aorta (aortography) is a reference method for diagnosing aortic dissection.

Treatment of aortic dissection

Tactics of treatment of patients with aortic dissection is different depending on the duration of the dissection and its location. Acute aortic dissection occurs up to 2 weeks from the onset of the disease, chronic aortic dissection occurs after this period. If an aortic dissection is suspected, the patient should be urgently taken to the hospital on a stretcher, where he will continue to be prescribed strict bed rest. Any physical stress can lead to irreversible consequences. Dissection of the ascending aorta and arch due to the possibility of life-threatening complications in most cases is an absolute indication for emergency surgery, regardless of the statute of limitations of the dissection. In the case of dissection of the descending and abdominal aorta in the absence of an immediate threat to life, the operation can be performed in a planned manner.

Indications for emergency surgery for dissection of the descending and abdominal aorta are the threat of further dissection or incipient rupture of the aortic wall with internal bleeding. An additional argument in favor of performing the operation in such patients is the development of an aortic aneurysm or a progressive dysfunction of the chest and abdominal organs, in particular, the kidneys.