The inflammatory phases of Atherosclerosis The WritePass Journal

The inflammatory phases of Atherosclerosis Abstract The inflammatory phases of Atherosclerosis Abstract IntroductionAimsRationale of the aimsRelated Abstract Aim This review describes recent investigations in to the impact of atherosclerosis on the vessel using four inflammatory stages eventually leading to cardiovascular complication. Research in to atherosclerosis has intensified globally as it has become one of the main reasons for increased mortality among individuals particularly within western societies. Inflammation has been established as the principal concept due to it stimulating progressive lesion development. As a result it is known as a chronic inflammatory disorder. Numerous cellular and molecular inflammatory mediators participate in the formation, development and rupture of the atherosclerotic plaque. Several experimental studies have demonstrated that monocyte- derived macrophages as well as T-lymphocytes are the most distinctive cells to accumulate within progressive plaques and induce the production of pro-inflammatory components, more recently, potential anti-inflammatory mediators have been identified in the inflammatory response. The rate of progressive plaque development varies in different types of people. Risk factors increase the development of this condition and promote the occurrence of physical symptoms on the patient. Conclusions (1) Inflammation attacks arteries systematically within phases and (2) the significance of the role of inflammatory molecules, linking inflammation to atherosclerosis. Introduction The management of cardiovascular diseases has significantly improved, however it is still not clearly understood as to why atherosclerosis remains the leading pathological cause of both morbidity and mortality in developed countries. Atherosclerosis is known to be a type of arteriosclerosis, but in addition to the hardening and narrowing of the arteries, cholesterol begins to deposit within their walls. It is a multifactorial disease which includes build up of atheromatous plaque and accumulation of more complex lesions within the arterial walls specifically in the intimal layer leading to the rupture of these vulnerable atherosclerotic plaques (Skjot-Arkil et al, 2010). This process is initiated in childhood and according to the results of PDAY   (pathobiological determinants of atherosclerosis in youth study), visible symptoms of atherosclerosis will occur between ages of 15-54 years (McGill et al.2007). Furthermore this disease can occur in both medium and large sized arteries including the aorta, carotid artery and even the smaller coronary arteries. Due to the fact that it affects multiple arterial locations, it can then lead to clinical diseases such as coronary artery disease, cerebrovascular disease, myocardial infarction. Jongstra et al. (2006) demonstrated that within the intima of VCAM-1 positive mice, local chronic inflammation predisposed to atherosclerosis. This provided further evidence to support previous studies that inflammation participates in the atherosclerotic process. Consequently, inflammation is progressively involved in the plaque formation, resulting in an inevitable stenosis (Vidal-Vanaclocha, 2009). Numerous epidemiological studies have revealed many risk factors that accelerate atherosclerosis development including age, male gender, obesity, smoking, hypertension and diabetes mellitus. Moreover, a recent study (Holvoet et al, 2007) found that a positive correlation exists between an increased amount of oxidised LDL and the quantity of calcium built up in the coronary artery. Therefore showing that increased amount of oxidised LDL is a unique risk factor for the development of atherosclerosis. The factors that facilitate this plaque formation are inflammatory mediators. As the endothelial cell is activated, this results in expression of many cell surface adhesion molecules including cytokines, chemokines, monocytes, immunoglobulins. These promote endothelial dysfunction in atherosclerosis as well as inducing foam cell formation with the assistance of macrophages. However, the functional mechanisms of cytokines in initiating and prolonging atherosclerosis are still not clearly un derstood. Aims To explore the role of inflammation in atherosclerosis To explore the mechanisms of inflammatory cell recruitment and accumulation within the plaque. To explore the function of various different mediators in this process, including both pro and anti-inflammatory mediators. Rationale of the aims To investigate the effects of the inflammatory cycle on arteries using atherosclerosis as the central condition. Hence, following the aims and objectives of the literature review, an overview of numerous meta-analyses of mediator involvement in this process is provided. This would be performed by reviewing the most relevant literature for the past five years using Pubmed, Science direct and Google Scholar. Table 1 Methodical reviews on the involvement of inflammatory components within the development of atherosclerosis. Type of component Mediator Experimental source Inflammatory effect Effect on Atherosclerosis Author, year Immunoglobulin ICAM-1 Human plasma Human aortic SMC Human aortic endothelial cells ↑ ↑ ↑ ↑ ↑ ↑ Bielinski et al, 2008 Burton et al, 2009 Roth et al, 2007 Immunoglobulin VCAM-1 Human plasma Human aortic endothelial cells ↑ ↑ ↑ ↑ Bielinski et al, 2008 Roth et al, 2007 Cytokine TNF-alpha APoE-/- mice ↓ ↓ Bhaskar et el, 2011 Cytokine IFN-gamma Human RNA ↑ ↑ Niedzielska and Cierpka, 2010 Cytokine M-CSF Human platelets ↑ Siezer et al, 2010 Cytokine IL-6 Human aortic endothelial cells Human Plasma APoE-/- mice ↑ ↑ ↓ ↑ ↑ ↓ Roth et al, 2007 Hoshi et al, 2008 Bhaskar et al, 2011 Cytokine IL-1 (beta) Human aortic SMC APoE-/- mice ↑ ↑ ↑ ↑ Burton et al, 2009 Bhaskar et al, 2011 Chemokine CXCL16 Human and murine   macrophages APoE-/- ↑ ↑ ↑ Lehrke et al, 2007 Wen-Yi et al, 2011 Chemokine CXCR6 Human and murine macrophages ↑ ↑ Lehrke et al, 2007 Ligand CD40 L Human umbilical vein endothelial cells ↑ ↑ Chakrabarti et al, 2010 Monocyte Protein MCP-1 Human aortic endothelial cellsAPoE-/- mice ↑ ↓ ↑ ↓ Roth et al, 2007 Bhaskar et al, 2011 Toll-like receptor TLR-2 ↑ Doherty et al, 2006

Battle of Badajoz - Peninsular War

Battle of Badajoz - Peninsular War Battle of Badajoz - Conflict: The Battle of Badajoz was fought from March 16 to April 6, 1812 as part of the Peninsular War, which was in turn part of the Napoleonic Wars (1803-1815). Armies Commanders: British Earl of Wellington25,000 men French Major General Armand Philippon4,742 men Battle of Badajoz - Background: Following his victories at Almeida and Ciudad Rodrigo, the Earl of Wellington moved south towards Badajoz with the goal of securing the Spanish-Portuguese frontier and improving his lines of communication with his base at Lisbon. Arriving at the city on March 16, 1812, Wellington found it held by 5,000 French troops under the command of Major General Armand Philippon. Long aware of Wellingtons approach, Philippon had significantly improved the Badajozs defenses and had laid in large supplies of provisions. Battle of Badajoz - The Siege Begins: Outnumbering the French nearly 5-to-1, Wellington invested the city and began construction of siege trenches. As his troops pushed their earthworks towards Badajozs walls, Wellington brought up his heavy guns and howitzers. Knowing that it was only a matter of time until the British reached and breached the citys walls, Philippons men launched several sorties in an attempt to destroy the siege trenches. These were repeatedly beaten back by British riflemen and infantry. On March 25, General Thomas Pictons 3rd Division stormed and captured an outer bastion know as the Picurina. The capture of the Picurina allowed Wellingtons men to expand their siege works as his guns pounded away at the walls. By March 30, breaching batteries were in place and over the next week three openings were made in the citys defenses. On March 6, rumors began to arrive in the British camp that Marshal Jean-de-Dieu Soult was marching to relieve the beleaguered garrison. Wishing to take the city before reinforcements could arrive, Wellington ordered the assault to commence at 10:00 PM that night. Moving into position near the breaches, the British waited for the signal to attack. Battle of Badajoz - The British Assault: Wellingtons plan called for the main assault to be made by the 4th Division and Craufurds Light Division, with supporting attacks from the Portuguese and British soldiers of the 3rd and 5th Divisions. As the 3rd Division moved into place, it was spotted by a French sentry who raised the alarm. With the British moving to attack, the French rushed to the walls and unleashed a barrage of musket and cannon fire into the breaches inflicting heavy casualties. As the gaps in the walls filled with British dead and wounded, they became increasingly impassable. Despite this, the British kept swarming forward pressing the attack. In the first two hours of fighting, they suffered around 2,000 casualties at the main breach alone. Elsewhere, the secondary attacks were meeting a similar fate. With his forces halted, Wellington debated calling off the assault and ordering his men to fall back. Before the decision could be made, news reached his headquarters that Pictons 3rd Division had secured a foothold on the city walls. Connecting with the 5th Division which had also managed to scale the walls, Pictons men began pushing into the city. With his defenses broken, Philippon realized that it was only a matter of time before British numbers destroyed his garrison. As the redcoats poured into Badajoz, the French conducted a fighting retreat and took refuge in Fort San Christoval just north of the city. Understanding that his situation was hopeless, Philippon surrendered the following morning. In the city, British troops went wild looting and committed a wide array of atrocities. It took nearly 72 hours for order to be completely restored. Battle of Badajoz - Aftermath: The Battle of Badajoz cost Wellington 4,800 killed and wounded, 3,500 of which were incurred during the assault. Philippon lost 1,500 dead and wounded as well as the remainder of his command as prisoners. Upon seeing the piles of British dead in the trenches and breaches, Wellington wept for the loss of his men. The victory at Badajoz secured the border between Portugal and Spain and allowed Wellington to begin advancing against the forces of Marshal Auguste Marmont in Salamanca.