However, Onat et al. Evidence is further beginning to emerge that the antioxidant and atheroprotective functions of ApoA-1, become impaired in the process of autoimmune activation. Such impairment could be linked to excess circulating lipoprotein a and its oxidized phospholipids, and could represent a common denominator underlying various different chronic diseases.
Thus, it is time to recognize that the clinical significance of HDL cholesterol concentrations in the general population is markedly heterogeneous, and high concentrations do not necessarily imply reduced cardiometabolic risk.
Evidence is presented that enhanced systemic inflammation, or oxidative stress associated with elevated plasma triglyceride rich lipoproteins and their remnants, and excess oxidized lipoA phospholipids underlie this risk. The adverse risk profile is augmented by loss of the anti-inflammatory, antioxidative and atheroprotective properties of HDL and its apoprotein.
Common clinical manifestations are atherogenic dyslipidemia and hypertriglyceridia with elevated ApoB or hypertriglyceridemic waste phonotype. Much research is needed on this topic to further clarify the impact of ApoA-1 dysfunction to elucidate the underlying genetics and mechanisms and to determine preventive measures and optimal managements. Ox-LDL activates T cells and macrophages, stimulates the expression of adhesion molecules, attracts macrophages to sarcoplasmic reticulum, and produces foam cells.
Oxidation of LDL and its containing cholesterol have an important role in formation of atherosclerotic plaques. The starting point of this process is the damage caused by combination of unsaturated lipids of plasma or arterial membrane with oxygen or side products of their oxidation. These receptors attract them more strongly in the way that cholesterol accumulates in macrophages to form foam cells. Low density lipoprotein is composed of an ester cholesterol core surrounded by lipophilic antioxidants and phospholipids.
Lipophilic antioxidants initially preserve LDL particle against deformation, however after antioxidants lowering, unsaturated fatty acids will be oxidized. In this step of oxidation that is associated with small amount of oxidized lipid products and unchanged ApoB protein, LDL particle undergoes some slight changes.
If these steps continue and lipid oxidation products accumulate largely in LDL particle, these materials start reacting with amino acids of ApoB protein and change them by covalent bond formation, which results in LDL's negative charge increase and degradation of their protein part.
The result is creating new binding sites to the collecting receptor. LDL oxidation is a process with free radicals in which unsaturated lipids convert to lipid peroxides by lipid peroxidation and then change to aldehyde products such as malondialdehyde MDA , hexanone and other compounds. The produced aldehydes bond with amino groups of ApoB Malondialdehyde-LDL is attracted to monocyte derived macrophages and produce foam cells. This is one of the compounds that will be formed during lipid peroxidation.
One of the side-effects of Ox-LDL formation is vascular contraction. Meanwhile, lipid peroxides accelerate plaque formation by inhibiting prostacyclin synthesis as a strong inhibitor of platelets aggregation. Oxidation also converts phosphatidylcholine to lysophosphatidylcholine and produces sterols from cholesterol esters in lipid core of LDL. Ox-LDL has many effects such as monocytes chemotaxis, inhibition of macrophages movement, fat cells formation, more expression of endothelial adhesion molecules, growth factor stimulation, chemokine expression, monocytes proliferation, fatty streaks formation, and thickening of intima that is effective in the initial progress of atherosclerosis.
Malondialdehyde is the final product in lipid especially LDL peroxidations. This compound is an active aldehyde as well as an active type of electrophiles, which can cause toxic stress in cells and advanced glycation end-products. This aldehyde's product is a biomarker for measuring stress oxidative level. Hypertension is a risk factor in cardiovascular diseases and stroke.
These complications are generally caused by high diastolic blood pressure. Hypertension damages endothelium by increasing the hemodynamic pressure on endothelium and may increase the permeability of arterial walls for lipoproteins. Hypertension is correlated with the increased risk of myocardial infarction.
Although, the complications of hypertension were formerly attributed to diastolic blood pressure, there is much evidence showing that systolic blood pressure plays a role as well. The mechanism with which hypertension can accelerate atherosclerosis is still unknown; however, in animals fed with high fat, hypertension accumulates the fatty substances inside the arterial walls.
There is endothelium related vasodilation in atherosclerotic vessels even before changes in the vascular structure, which shows decreased eNOS. It has been demonstrated that in special pathologic conditions such as severe hypercholesterolemia, malfunctioned eNOS, and peroxynitrite are produced instead of NO. Dysfunction of eNOS causes vascular dysfunctions such as atherosclerosis.
All the effective risk factors of atherosclerosis such as hyperlipidemia, diabetes mellitus, hypertension, and cigarette smoking are related to the damaged endothelium. There are reports about endothelium regeneration by antioxidants and superoxide dismutase, which shows the importance of superoxide in the damaged endothelium.
Antioxidants can heal the damaged endothelium in human and animal models of atherosclerosis. There are some evidence suggesting that eNOS is an anti-atherogenic factor. Furthermore, chronic consumption of L-Arginine eNOS substrate can prevent atherosclerosis in animals. Nitric oxide is produced in the endothelium and rapidly leaks to reach to the molecular targets in the vascular walls and vascular channels.
It can react with transcription factors such as protein I activator and KB nuclear factor. It also inhibits the expression of inducing thrombin of platelet activating factor. Nitric oxide has also anti-proliferating effect, and can potentially inhibit the proliferation, migration, and extracellular matrix synthesis. It has anti-inflammatory effects, too. Nitric oxide prevents translocation of KB factor, blocks the cytokine stimulated expression of endothelial adhesion molecules and decreases neutrophils and monocytes activity[ 58 ] [ Figure 4 ].
It is also elevated in patients with unstable angina. CRP, a marker for acute-phase of inflammation, predicts early and late mortality in patients with acute coronary syndromes. CRP itself promotes inflammation[ 62 , 63 , 64 ] and atherogenesis through effects on monocytes and endothelial cells and increases the activity and concentration of plasminogen activator inhibitor-1 PAI There is some evidence showing that inflammatory markers are also related to coronary artery disease.
For example, CRP shows more predictive information than what other documented risk factors such as cholesterol do. Increased levels of acute-phase reactants such as fibrinogen and CRP can reflect the extravascular inflammation, which can intensify the atherosclerosis and its complications. Nevertheless, both factors are effective in increasing the inflammatory markers in patients prone to coronary artery disease. C-reactive protein is a member of pentraxin proteins family.
It is an acute-phase reactant, which releases after infection, acute injury, or other inflammatory stimulations. C-reactive protein is a plasma protein which is very similar in both vertebrates and invertebrates.
CRP may have a role in any of these steps through effective direct processes such as complement system activation, absorption, activity, and cellular modulation, lipid accumulation and thrombosis. Thrombosis is also effective for developing atherosclerotic damage and accelerating the cardiovascular events. Direct activities of CRP for conducting the pro-thrombotic stage include; reinforcement of precoagulative activity[ 76 ] or reduction of fibrinolysis. C-reactive protein induces platelets binding to endothelial cells[ 78 ] and stimulates monocytes and lymphocytes absorption into endothelial walls.
CRP intermediates the proliferation and activities of vascular SMC, which leads to accumulation of these cells in the vascular intima that is a key factor in advancing vascular wall damage. C-reactive protein is a factor related to lipoprotein deposition and complement system activity in atherosclerotic plaques. It amplifies the activity of compliment system, which particularly in the first steps of atherosclerosis may lead to development and advancement of atherosclerotic damage.
Mediators of acquired and innate immunity are involved in atherosclerosis, as might be anticipated for a chronic inflammatory process. Innate immune reactions against viruses and bacteria have been included in the list of pathogenic factors in atherosclerosis. Acute respiratory infection might be a risk factor for myocardial infarction. An increase in acute coronary diseases during winter infections and flu epidemics has been related to seasonal variations in factor VIIa and fibrinogen, probably induced via activation of the acute-phase response.
The humoral immune response might be a risk factor for coronary heart disease, inducing inflammation that links immunity with coronary disease.
Immune reaction and infection cause endothelial dysfuction, cell injury and a pro-inflammatory environment. IL gene expression is stimulated by lipopolysaccharides and pro-inflammatory cytokines. Infection is also a trigger of IL There is a relationship between the patho-physiology of ischemic heart disease and infection as well as the severity of atherosclerosis.
Furthermore, viral and bacterial proteins can induce anti-phospholipid antibody production in humans which might be an additional factor attacking endothelium. It might participate in the acute coronary process through a direct effect on atheroma and initiate the inflammatory process, subsequently being activated during inflammation and acutely exacerbating the response. The controversial role of C. Controversial results could be related to these different anti-inflammatory effects.
Currently, fibrinogen and factor VII homeostatic factors are known as confounding risk factors in cardiovascular diseases. There is a relationship between plasma fibrinogen level or PAI-1 as a fibrinolysis inhibitor and the risk of coronary artery diseases. Fibrinogen is a circulating glycoprotein which has activity in coagulation steps responding to tissue and vascular damage.
In addition to thrombotic role, fibrinogen causes cellular proliferation,[ 91 ] contraction of damaged cellular walls, stimulation of platelet aggregation,[ 92 ] and regulation of cell adhesion. Fibrinogen participates in inflammation and thrombosis.
Fibrinogen is probably less affected by inflammatory stimulation compared with CRP and consequently is a specific marker. Fibrinogen increase in patients with atherosclerosis can be a secondary phenomenon, although it participates in lesion formation and thrombosis. Factor VII is also a coagulative protein, which has an important role in thrombogenesis. Several studies demonstrate the correlation between factor VII and inflammatory factors such as IL-6 and CRP in patients with hypercholesterolemia, which shows their pathophysiologic correlation.
There are also some reports showing the correlation between coagulation system constituents fibrinogen and factor VII or fibrinolytic factors tissue plasminogen activator, PAI and atherosclerosis[ 96 ] [ Figure 5 ].
Furthermore, several plant with antioxidant activity have been shown to decrease the fibrinogen and factor VII levels even more than statins. Although homocysteine does not seem to be a strong predictor of athrosclerosis, Cavalca et al. Impaired homocysteine metabolism may result in oxidative stress,[ ] which can play a role in hyperhomocysteinemia-mediated vascular disorders. Trace amounts of antioxidants are able to protect cell membranes and other body compartments against oxidants.
Antioxidants are able to prevent diseases such as Alzheimer,[ ] seizure, cancer,[ , ] aging,[ ] and atherosclerosis[ , ] by reducing the effects of free radicals.
Producing reactive oxygen species ROS in cells is a natural process. This production can be amplified in different pathophysiologic conditions such as inflammation, immunologic diseases, drug and alcohol metabolism, ultraviolet ray or radiotherapy, and antioxidant vitamins deficiency. Uncontrolled ROS release usually damages cellular macromolecules such as deoxyribonucleic acid, protein, and lipid. Inhibiting free radicals production by metal ions chelating agents peroxide decomposition.
Breaking the reaction chain to inhibit hydrogen absorption by activated radical. In vitro peroxidation is affected by activity of enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Since lipid peroxidation is considered as the key event in atherosclerosis, antioxidant protection is often related to preventing lipid peroxidation.
Therefore, reduction of lipoproteins oxidative change in the body by natural and synthetic antioxidants is an effective way to prevent cardiovascular disorders. Rapid advancements in understanding the molecular mechanisms of atherosclerosis have led to discover and suggest mechanisms to postpone the progress of coronary artery disease. Antioxidants such as vitamin E, selenium, beta-carotene and chemical compounds such as butyl hydroxytoluene and butyl hydroxyanisol can prevent cell membrane oxidation.
Therefore, studies on some natural compounds with antioxidant properties without toxic effects to inhibit lipid peroxidation and consequently to prevent related diseases seem necessary. Several studies have demonstrated that receiving a mixture of specific antioxidants as food supplements decrease the production of MDA and protein carbonyl, decrease erythrocyte hemolysis, and increase the total amount of antioxidants.
Medicinal herbs, as a source of different antioxidants, can be very effective in modulating oxidative stress derived cardiovascular or renal damages. Flavonoids are a group of phenolic compounds with low molecular weights. Their basic structure is similar and found in fruits and vegetables. The amount and type of flavonoids in different plants depend on the species, growth, and maturity of the plants.
More than phenolic structures are known which are composed of various molecules such as phenolic acids to fully polymerized compounds such as tannins.
They are classified in flavonoid main groups comprising anthocyanins, flavonols, flavones, neoflavones, isoflavones, and dihydroflavones. Flavonoids are among potent antioxidants, free radical scavengers, metal excreters, ROS-family compounds collector, and lipid peroxidation inhibitors. Studies show that flavonoids inhibit LDL oxidation in macrophage culture media and also reduce Ox-LDL absorption by macrophage sweeping receptors.
Considering the therapeutic effect of flavonoids for cardiovascular diseases, using plants with such effects seems necessary. Various studies with promising results have been done on plants with such properties. The most important medicinal herbs with documented antioxidant activity and hypolipidemic effects are as follows.
Arachis hypogaea, Citrus limon, Linum usitatissimum, Aloe littoralis, Aloe vera, Ziziphus jujube, Zingiber officinale, Onopordon acanthium, Celosia cristata, Mukul comiphora.
Atherosclerosis starts with fatty streaks formation and progresses with atheroma and atherosclerotic plaque formation. Lipid oxidation, in the form of Ox-LDL, demonstrates the first step of atherosclerosis. MDA shows lipid peroxidation level and is a marker of increased oxidative stress.
CRP is an indicative marker of body's response to inflammatory processes. It is one of the most important pathogenesis factors along with fibrinogen in atherogenic processes.
Nitric oxide is known as a vasodilator and endothelial survival factor which enhances the endothelial cell proliferation and migration. In special pathologic conditions such as severe hypercholesterolemia, peroxynitrate concentration increases, which leads to severe atherosclerotic damage.
Considering the role of oxidative stress and lipid oxidation in formation and progress of atherosclerosis and endothelial damage, using antioxidants, especially herbal types can be beneficial.
Conflict of Interest: None declared. National Center for Biotechnology Information , U. Int J Prev Med. Author information Article notes Copyright and License information Disclaimer. Correspondence to: Dr. E-mail: moc. Received Jan 5; Accepted Mar 4.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. This article has been cited by other articles in PMC.
Abstract Background: Atherosclerosis is the major cause of morbidities and mortalities worldwide. Methods: The recently published papers about atherosclerosis pathogenesis and herbal medicines effective in the treatment and prevention of hyperlipidemia and atherosclerosis were searched.
Results: Inflammation has a crucial role in pathogenesis of atherosclerosis. Conclusions: The pathogenesis factors involved in atherosclerosis have recently been cleared and the discovery of these factors has brought about new hopes for better prevention and treatment of atherosclerosis. Keywords: Atherosclerosis, inflammation, lipids. METHODS The recently published papers about atherosclerosis pathogenesis and herbal medicines effective in the treatment and prevention of hyperlipidemia and atherosclerosis were searched in databases such as Web of Science, Medline, PubMed, Scopus, Embase, Cinhal and the Cochrane from to Fatty streaks formation Both animal and human studies show that the fatty streaks are the first sign of atherosclerosis.
Open in a separate window. However, when a major artery is blocked, signs and symptoms may be severe, such as those occurring with heart attack, stroke, or blood clot. The symptoms of atherosclerosis may look like other heart conditions. See your healthcare provider for a diagnosis. First, your doctor will do a complete medical history and physical exam.
You may also have one or more of these tests:. Cardiac catheterization. With this procedure, a long thin tube catheter is passed into the coronary arteries. X-rays are taken after a dye is injected into an artery to locate the narrowing, blockages, and other abnormalities of specific arteries.
Doppler sonography. A special probe is used to direct sound waves into a blood vessel to evaluate blood flow. An audio receiver amplifies the sound of the blood moving though the vessel. Faintness or absence of sound may mean there is a blockage. This is used to identify narrowing of the blood vessels of the abdomen, neck, or legs.
Blood pressure comparison. Comparing blood pressure measurements in the ankles and in the arms helps determine any constriction in blood flow. Significant differences may mean blood vessels are narrowed due to atherosclerosis. This is a nuclear scan to see how the heart wall moves and how much blood is expelled with each heartbeat, while the person is at rest.
This is a nuclear scan given while the person is at rest or after exercise that may reveal areas of the heart muscle that are not getting enough blood.
Jung J, et al. Epidemiology, risk factors, pathogenesis and natural history of abdominal aortic aneurysm. Arnett DK, et al. Whelton PK, et al. Effectiveness checker: High cholesterol. Natural Medicines. Effectiveness checker: Atherosclerosis.
Effectiveness checker: Hypertension. Mitchell EL, et al. Noninvasive diagnosis of arterial disease. Wilson PWF, et al. American Journal of the American College of Cardiology. Tapson VF. Approach to thrombolytic fibrinolytic therapy in acute pulmonary embolism: Patient selection and administration. Riggin EA. Allscripts EPSi. Mayo Clinic. Coronary calcium scan. De Lemos J, et al. Elsevier; Atherosclerosis can affect arteries in other parts of the body, such as the pelvis and legs, causing poor circulation.
Abdominal aortic aneurysm. Atherosclerosis can make the walls of the aorta weak. The aorta is the large artery that carries blood from the heart to the rest of the body. A major part of treating atherosclerosis and coronary artery disease involves lifestyle changes such as quitting smoking and medicines to help reduce high cholesterol, control high blood pressure, and manage other things that increase a person's risk of heart attack, stroke, and other complications.
If you think of atherosclerosis as a response to injury, the buildup of fibrous plaque can be reversed by removing the source of injury.
In the case of high cholesterol, by reducing the amount of LDL cholesterol in your arteries and increasing the amount of HDL—which removes cholesterol that is already in your artery walls—you can actually reverse atherosclerosis. The ability to reverse atherosclerosis helps explain why treating high cholesterol can reduce the risk of further complications from atherosclerosis. Although the exact process is not completely understood, scientists have described three different stages of atherosclerosis that lead to clogged arteries.
These stages do not necessarily occur in order, nor is there always a progression from one stage to the next. The fatty streak. The "fatty streak" appears as a yellow streak running inside the walls of the major arteries, such as the aorta. The streak consists of cholesterol, white blood cells, and other cellular matter. The fatty streak by itself does not cause symptoms of heart disease but can develop into a more advanced form of atherosclerosis, called fibrous plaque. The plaque. A plaque forms in the inner layer of the artery.
Plaque is a buildup of cholesterol, white blood cells, calcium, and other substances in the walls of arteries. Over time, plaque narrows the artery, and the artery hardens. Plaque sometimes reduces blood flow to the heart muscle, which can cause angina symptoms.
Plaque in the large artery in the neck carotid artery stenosis may block blood flow to the brain and is a common cause of transient ischemic attack sometimes called "mini-stroke" and stroke. Plaques are covered with a fibrous cap, which may rupture if some trigger causes a surge in blood pressure or causes the artery to constrict. A person may have a heart attack if a plaque breaks open, creating a blood clot that completely blocks blood flow through the artery.
Complicated lesion.
0コメント