BME 792 Courtney Kinser
Term Paper 05/04/18
Abstract
Statins are currently the gold standard in treatment of atherosclerosis, with the aim of reducing serum low density lipoprotein levels. However, recent research supports atherosclerosis as a complex inflammatory condition, with the benefits of statins being partially attributed to their effects on smooth muscle cells, plaque stability and endothelial function, as well as their involvement in macrophages and the inflammatory response. Traditionally used as anti-cancer drugs for their anti-inflammatory effects, proteasome inhibitors are now being recognized for their therapeutic potential in this area. A shift in the treatment approach for atherosclerosis from reduction of serum cholesterol
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CAD can lead to coronary heart disease (CHD) which presents diagnoses of angina pectoris, myocardial infarctions, and silent myocardial ischemia, often leading to death or disability. CHD is responsible for roughly one-third of deaths in people over the age of 35, with current trends projecting that CHD-related mortality rates will continue to rise in developing countries (Sanchis-Gomar et al.).
The pathogenesis of atherosclerosis is a dynamic process which involves inflammation, oxidative stress, proliferation, and cell apoptosis. These processes are regulated by the ubiquitin proteasome system (UPS), and have also been shown to influence UPS activity and function (Wilck). My current research involves cell migration studies of primary mouse vascular aortic smooth muscle cells under various drug treatments. Treatments include a statin (Fluvastatin), oxidized low density lipoprotein (oxLDL), and a proteasome inhibitor (Bortezomib). The aim of this proposed research is to further investigate the role of the ubiquitin proteasome system in primary vascular aortic smooth muscle cells under varying drug treatments. Such a study provides insights regarding the treatment of atherosclerosis as well as the progression of hyper- and hypocholesterolemia related diseases. It is hypothesized that the UPS will have increased activity
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The development of an atheroma occurs following an injury to the endothelial lining, the tunica media, of the artery. This inflammatory environment releases chemotactic agents and growth factors, prompting the transport and modification of plasma lipids. This event is favorable towards low-density lipoproteins which oxidize within the inflammatory environment, delivering cholesterol to and damaging surrounding cells. Macrophages arrive and uptake the LDL’s, transforming into foam cells which collectively form a fatty streak. Migration of smooth muscle cells from the tunica media form a fibrous cap construct of elastic and collagen fibers. This fibrous cap thickens the intima layer, eventually reducing the lumen area of the vessel. As the smooth muscle cells, macrophages, and foam cells contained in the plaque die, calcium deposits develop and collagen production ceases, yielding the plaque susceptible to a rupture event
Coronary artery disease is a heart disease characterized by narrow arteries and restricted blood flow in arteries and is the major cause of morbidity and mortality globally.[1] According to WHO estimation, 6.8% in men and 5.3% in women are affected globally.[2-4] Cardiovascular disease account for 29% of all deaths in Canada; of all the cardiovascular death, 54% and 23% was due to ischemic heart disease and heart attack, respectively. The total costs for heart disease and stroke were more than $20.9 billion every year. [5,6] With more than 1 artery impacted, multivessel coronary artery disease is more complex and more likely accompanied by other comorbidities including diabetes or high blood pressure; multivessel coronary artery disease usually is more difficult to deal with, has worse prognosis and cost more compared with single coronary artery disease. [7]
Atherosclerosis is a pathological condition that underlies several important adverse vascular events such as stroke, cerebrovascular disease, Coronary Artery Disease (CAD). etc. [1]. It is responsible for most of the cardiovascular morbidity and mortality in the Western World currently [2]. As a result of the adoption of the western life style, its prevalence is increasing all over the world and could likely reach epidemic status in the coming future [2]. Atherosclerosis is a chronic disease of the arterial wall whose underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response involving chronic inflammation of the arterial wall [1]. Leukocyte trafficking shapes the disturbed equilibrium of lipid accumulation, immune responses and their clearance and homeostasis, and this leukocyte trafficking is governed by chemokines and their receptors [1]. Chemokines are a superfamily of small structurally related chemotactic cytokines, which are involved in leukocyte trafficking and activation [3]. Chemokines have been found to play major roles in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors [4]. Additionally, chemokines and their receptors have been identified as key players in the progression of atherosclerosis, thus they are explored in order to find therapeutic targets to prevent or treat Atherosclerosis and by targeting the chemokine system various entry points for a causative treatment are offered [5]. In this essay, the role of chemokine system in atherosclerosis is visited, the strategies employed to target chemokines as a therapeutic pathway for atherosclerosis and clinical trials undertaken ...
An artery is an elastic blood vessel that transports blood away from the heart. There are two main types of arteries: pulmonary arteries and systemic arteries.
LDL or bad cholesterol comes from food that is a high source of cholesterol and/or saturated fats. Plaque forms when bad or LDL cholesterol builds up in your bloodstream and attaches to the arterial wall, as more LDL builds up the plaque becomes larger, this can become a major problem for your cardiovascular system. Because plaque is a substance that has rough edges, it reduces the elastic nature of the artery which means your heart will have to work double-time to pump the necessary blood to all your limbs, that will mean your limbs won’t get the amount of oxygen that they require to function properly. Plaque can also narrow the area blood has to pass through, this means your heart has to work overtime and overall capacity of your cardiovascular system is lowered. When the LDL cholesterol embeds itself in the wall of the artery it than damages the artery then blood pressure expands it which causes an aneurysm. When an aneurysm is too weak there is a high possibility of it bursting, when that happens it leaves the cells in and around that area without oxygen. If that artery is connected to a major vital organ the person will most likely die. When the blood flow is slowed it shows a greater risk for blood clots and although blood clots are natural and important to healing broken blood vessels, if blood clots gather inside the blood vessel this proves to be a serious health risk. The clots have the possibility to get stuck and completely cut off the blood flow to cells, leaving them without oxygen and causing them to die. If a clot gets inside a blood vessel connected to a major organ this could cause the person to die. The heart is fed by the coronary artery, if plaque or a blood clot blocks off blood flow to the heart, the heart ...
The walls of arteries are made up of three layers same as veins. Its inner endothelium is composed of epithelial cells which is very smooth. This layer helps minimise the friction. The tunica media provides strength and elasticity. It contains smooth muscles, collagen and large amount of elastic fibres.
Atherosclerosis begins when the inner wall of the artery becomes damaged and cholesterol and fatty plaques begin to lodge in the arteries. Damage to the endothelial wall inside the artery can be caused by hypertension, hyperlipidemia, and hyperglycemia (“Subclinical Atherosclerosis..” 443). When this happens, the immune system responds by sending monocytes to the damaged area. The monocytes turn into macrophages; their job is to eat up the excess cholesterol and unblock the artery. The macrophages are unable to digest all of the cholesterol, and as a result turn in to foam cells. When many macrophages are turned into foam cells, plaque results, and protrudes into the arterial wall, restricting blood flow and raising blood pressure (“Atherosclerosis Growth Process.” 8). If the plaque becomes too large it may break, releasing plaque into the blood. This can cause a great reduction in blood flow or a clot, resulting in stroke or myocardial infarction (“Stroke Risk.” 3).
The preliminary step in myocardial infarction is atherosclerosis. Atherosclerosis does not occur abruptly, it is a gradual and dynamic inflammatory disease which causes the narrowing of lumen due to the deposition of lipid and foam cells. The formation of fatty streak; which will eventually become a plaque causes the vessel lumen to diminish. The plaque will become unstable, rupture and eventually lead to the event of plaque disruption.
Coronary artery disease (CAD) is the most common type of multifactorial chronic heart disease. It is a consequence of plaque buildup in coronary arteries. The arterial blood vessels, which begin out smooth and elastic become narrow and rigid, curtailing blood flow resulting in deprived of oxygen and nutrients to the heart [1].
Coronary heart disease is defined by the hardening of the epicardial coronary arteries. The buildup of plaque in the arteries slowly narrows the coronary artery lumen. In order to better understand the physiology of the disease, it is important to first know the basic anatomy of the human heart. The aorta, located in the superior region of the heart, branches off into two main coronary blood vessels, otherwise known as arteries. The arteries are located on the left and right side of the heart and span its surface. They subsequently branch off into smaller arteries which supply oxygen-rich blood to the entire heart (Texas Heart Institute, 2013). Therefore, the narrowing of these arteries due to plaque buildup significantly impairs blood flow throughout the heart.
Cardiovascular Disease is defined by the American Heart Association as “Heart and blood vessel disease”. Atherosclerosis of the arteries, can lead to hypertension, heart failure, arrhythmias, heart valve problems, myocardial infarctions or a stroke (AHA, 2016). In this paper, all of heart and vessel diseases aforementioned, will be considered cardiovascular disease (CVD). According to
Today, cardiovascular disease is “the number one killer in the United States and the developed world” (Sapolsky, 2004, p. 41). Coronary heart disease (CHD) is the most common form of cardiovascular disease, and is responsible for claiming an unreasonable amount of lives every year. CHD can begin to accumulate in young adults, but is prominently found in both men and women in their later adult lives. As a result of CHD, men typically experience heart attacks, whereas women present with chest pains, known as angina (Matthews, 2005).
Coronary heart disease or coronary artery disease affects 16.8 million people in the United States and causes more than 607,000 deaths annually (Lemone, chap.30). It is caused by atherosclerosis which is the accumulation of fatty deposits in the arteries causing impaired blood flow to the myocardium. CAD or coronary artery syndrome is usually without symptoms but may induce heart attack, angina and acute coronary syndrome if not properly treated. There are many risk factors associated with CAD like obesity, high cholesterol diet, hereditary, physical inactivity, just to name a few. Patients with CAD may be unable to identify and manage their risks factors. It is imperative for nurses to educate the patient about CAD and measures to enhance their health.
What is coronary heart disease (CHD)? It is a disease when plaque gets built up in the coronary arteries; and the job of the arteries are to provide rich-oxygenated blood to the heart muscle. Built plaque in the arteries leads to atherosclerosis and the plaque that is built can result from over the years. Throughout the years, the plaque tends to get hard or can rupture. If hardened, the arteries are now narrow and have weakened the flow of blood that travels to the heart. Blood clots can form from the plaque rupturing which can cause a great chance for the blood flow to be mostly blocked or blocked altogether. There are other names for coronary heart disease such as coronary artery disease, atherosclerosis, ischemic heart disease, etc.
of fatty substances on the inside wall of the arteries). It is not caused by
Etiology Myocardial infarction occurs when the coronary arteries are blocked by a blood clot. It is commonly known as a “heart attack”. The heart needs its own constant supply of oxygen and nutrients to work properly. Two coronary arteries deliver oxygenated blood to the heart, and if one of these two arteries fails or becomes blocked, then a portion of the heart will not acquire the necessary oxygen. This clot could be because of CAD (coronary artery disease), which happens when the inner walls of the coronary arteries thicken because of buildup of cholesterol, fatty deposits, calcium among other elements that are carried in the blood (Boston Scientific, 2009).