Involvement of the CHOP (CEBP Homologous Protein) in Atherosclerosis
Atherosclerosis is a medical condition characterized by the hardening and thickening of the arterial walls due to the accumulation of calcium and lipid materials. It is a condition that is recognized as a leading cause of a plethora of cardiovascular disease conditions. These range from strokes to heart attacks. Atherosclerosis often remains asymptomatic until one experiences the aforementioned cardiovascular problems. Through decades of research on this subject from a variety of different levels, it has been determined that the accumulation of fatty materials and maladaptive inflammatory responses in the arteries are major contributors in what leads to the progression of the disorder. Low density lipoproteins promote the accumulation of macrophages in the arteries and this further leads to inflammatory responses and arterial lesions in more advanced stages. The endoplasmic reticulum (ER) has been implicated as playing a major role in the progression of advanced stages of this disorder. There are two types of ER found within the cell, the rough ER and smooth ER. The rough ER contains ribosomes on its exterior and that is where protein synthesis occurs. The smooth ER does not contain ribosomes and plays the role of regulating lipid metabolism. The ER plays the role of properly folding proteins and secreting them to the golgi apparatus for use in other parts of the cell. It consists of a stack of flattened membranes referred to as cisternae. The lumen or cisternal space within the endoplasmic reticulum accounts for about 10% of the cell’s total volume. Within the phospholipid bilayer of this organelle is a major intracellular reservoir for calcium ions, steroid...
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..., the progression of the illness can be slowed. Although ER-stress related CHOP activity does not play a role in the initial stages of atherosclerosis, it leads to plaque progression and instability when expressed in macrophages in more advanced lesions. It has been observed in many experiments done on both humans and mice that a deficiency in CHOP actually reduces the progression of atherosclerosis. It leads to apoptosis in the macrophages by initiating the UPR through a variety of mechanisms. The UPR is something that is initiated only when there is undo ER-stress. The plaque formation and inflammation in arteries are the triggers that cue this stress in the ERs. Novel therapeutic treatments for the disorder are being developed through research that seeks to better understand the exact role of the CHOP proteins and the UPR in the progression of atherosclerosis.
Retrieved on March 2014 from world wide web at http://www.webmd.com/heart-disease/guide/heart-disease-heart-attacks Wolf, Zane Robinson & Hughes, Ronda G (n.d.). Error Reporting and Disclosure. Retrieved on March 2014 from world wide web at http://www.ncbi.nlm.nih.gov/books/NBK2652
...ve stress [8] and can help combat many cardiovascular disorders, thus confirming the protective capabilities of nitric oxide. Another one of nitric oxide’s protective capabilities stems from its role as a potent vasodilator, and these vasodilation properties are primarily achieved through the activity of eNOS. eNOS is a membrane bound protein that is classified as a calcium-calmodulin dependent enzyme [13]. At resting concentrations of calcium, eNOS generates low amounts of nitric oxide, however, as intracellular calcium concentration increases, there is a potent enhancement of nitric oxide production by eNOS [13], which then goes on to cause vasodilation to prevent blockage of blood flow. Due to its generally low output, eNOS is largely associated with basal cardiac function, while iNOS is a much higher output enzyme, generating much more nitric oxide than eNOS [5].
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.
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).
CAD is a leading cause of morbidity and mortality throughout the worldwide. The prevalence of biological and metabolic risk factors were also found to be high in development of coronary artery disease. Patients with hypercholesterolemia are at increased risk to experience cardiovascular events and to die from vascular disease [2]. .Statins, among the most commonly prescribed drugs worldwide, are cholesterol let downing agents used to manage cardiovascular and coronary heart diseases and to treat hypercholesterolemia. Statin’s therapy ...
Cardiovascular disease is currently the leading cause of death in the United States. It is responsible for one in four deaths every year, about 600,000 mortalities. This disease affects men and women, as well as every ethnic group. Coronary artery disease is the most common cardiovascular disease, representing approximately 400,000 deaths per year of the aforementioned 600,000 total deaths from cardiovascular diseases as a whole. In 2010 alone, coronary artery disease cost the United States $108.9 billion for health care services, medication, and lost productivity. These chilling statistics, published every year by the American Medical Association, demonstrate the immediate need for new and innovative ways to prevent, detect, and treat coronary heart disease. This paper will explore the molecular biology behind the disease while explaining the current treatments and prevention that are available today, why they work and what can be done to improve them.
Atherosclerosis is the culprit behind coronary heart disease (CHD) and stroke, which is the most common cause of death worldwide and in the United States10. Among the modifiable risk factors of CHD and stroke is the serum low density lipoprotein level (LDL)8, 11. Several randomized clinical trials have established that reducing the serum LDL level results in a reduction in the future risk of CHD and stroke in a linear relationship, in one study it was estimated that reducing the LDL by 1% would reduce the risk by 1.7 %.1-4, 7, 9, 13 Lipid altering drugs include several classes of medications each of which have their own mechanism of action. Statins inhibit HMG CoA reductase (hydroxymethylglutaryl CoA reductase), which is the rate-limiting enzyme for the production of cholesterol in the liver. Statins competitively inhibit this enzyme and induce an increased expression of LDL receptors in the liver.
It also helps in preventing heart disease and stroke by cleaning plaque in the arteries.
The cell plasma membrane, a bilayer structure composed mainly of phospholipids, is characterized by its fluidity. Membrane fluidity, as well as being affected by lipid and protein composition and temperature (Purdy et al. 2005), is regulated by its cholesterol concentration (Harby 2001, McLaurin 2002). Cholesterol is a special type of lipid, known as a steroid, formed by a polar OH headgroup and a single hydrocarbon tail (Wikipedia 2005, Diwan 2005). Like its fellow membrane lipids, cholesterol arranges itself in the same direction; its polar head is lined up with the polar headgroups of the phospholipid molecules (Spurger 2002). The stiffening and decreasing permeability of the bilayer that results from including cholesterol occurs due to its placement; the short, rigid molecules fit neatly into the gaps between phospholipids left due to the bends in their hydrocarbon tails (Alberts et al. 2004). Increased fluidity of the bilayer is a result of these bends or kinks affecting how closely the phospholipids can pack together (Alberts et al. 2004). Consequently, adding cholesterol molecules into the gaps between them disrupts the close packing of the phospholipids, resulting in the decreased membrane fluidity (Yehuda et al. 2002).
Atherosclerosis is the most common cause of CAD. Atherosclerosis is a progressive disease characterized by fat deposits in the arteries causing them to block the normal passage of blood. No one is quite sure how atherosclerosis develops. The plaque consists mostly of cholesterol, phospholipids and smooth muscle cells. They also reduce the size of the lumen of the affected artery which impairs the blood flow of this artery and later on could form a thrombus that will completely occlude the vessel. “Unfortunately, signs and symptoms of atherosclerosis usually don’t develop until at least 70% of an artery’s lumen has become obstructed. Angina is almost always the first symptom to appear.”(Journal: The killer behind CAD,2010). Modifiable factors that could prevent the occurrence of CAD include cigarette smoking, obesity, physical inactivity, atherogenic diet like diet high in cholesterol, use of contraceptive and hormone therapy replacement. “Women continue to ...
Coronary heart disease occurs when some of the arteries that carry blood to the heart muscle become narrowed with fatty deposits. In this condition fatty deposits called plaque, composed of cholesterol (see later) and fats, build up on the inner wall of the coronary arteries. When arteries are narrowed, the heart is not fully supplied with the oxygen and other nutrients it needs. If an artery is completely blocked, a heart attack occurs. Heart disease is very common.
...-1 (PAI-1) from the endothelial cells and monocytes, activating the extrinsic coagulation pathway. This also leads to activation of factor X and fibrin production.
of fatty substances on the inside wall of the arteries). It is not caused by
Innate system critical main defense is the cellular component; there are several kinds of cells involved in the process. One of the crucial cells is the macrophage. ...