ABSTRACT
Atherosclerosis has gained a lot of attention in cholesterol and heart related diseases and is of major concern in cardiovascular health. Most of the research previously conducted on atherosclerosis traced its root cause to high blood cholesterol levels. Emerging studies have drawn attention to immune response and inflammation as very important factors that augment the entire process of atherosclerosis. Research conducted over the years has thrown more light on inflammatory responses in atherosclerosis giving compelling evidences to suggest that inflammation is the key contributor to atherogenesis. Atherosclerotic lesions show similar features of inflammation as those found in typical inflammatory and auto immune disease such as rheumatoid arthritis. Experimental data and results from clinical trials have identified various risk factors including hypercholesterimia, obesity and infection together with biomarkers of inflammation such as C-reactive protein and Interleukin-18 to be associated with atherosclerosis. Most therapies for atherosclerosis produce anti-inflammatory effects. The most knowledge we have on atherosclerosis, the easier it would be to prevent or cure it entirely. This article reviews evidences that lend credence to the proposition that atherosclerosis is an inflammatory disease.
INTRODUCTION
It is predicted that in the next 15 years, cardiovascular diseases arising from atherosclerosis will be the major cause of death globally [1]; prevalence is high in most developed countries and some developing nations [1] and [2]. Cardiovascular disease contributes to 38% of the deaths in North America and is the primary cause of death in European men below the age of 65 while for the women, it falls into second category [1]. Atherosclerosis is the most significant underlying causes of heart failures, coronary artery disease, strokes and infarction (resulting from ischaemia of heart, brain or extremities) [3] and [1].
Atherosclerosis is derived from the Greek words ‘athero’ meaning paste and ‘sclerosis’ which means hardening. It can be described as an arterial disease characterized by the formation of atheromatous plaques (composed of cholesterol and macrophages) and the narrowing of the artery (stenosis). Atherosclerosis develops mainly in elastic and muscular arteries that are medium or large in size [4] and [1]. Inflammation is a biological process that occurs in response to stimulus arising from substances (pathogens, damaged cells, toxins, irritants) that pose threats to the survival of cells and the organism as a whole. It involves the immune system (which produces white blood cells to destroy the harmful stimulus) and the vascular system (aids in leukocyte transport into cells). Atherosclerosis develops due factors including failure of the immune system to counteract or destroy modified LDL, free radicals, infectious and or other harmful agents detected by the system as foreign or related diseased conditions [4-9]. The problem emanates from the inability of leukocytes (monocytes and T lymphocytes) to destroy or remove these foreign molecules resulting in the trigger of further immune response which causes the artery to become inflamed [7], [4], [8], [9] and [6]. Inflamed cells produce free radicals, which participate in cell degradation. Atherosclerotic lesions can remain asymptomatic for years and either disappears with time or progress into disease stages where clinical manifestations such as unstable angina pectoris and myocardial infarction can be observed [1] and [3]. Atherosclerosis is a chronic disease since it progresses over years and is cumulative.
In this review, we seek to fully elucidate the role and significance of inflammation in atherosclerosis by examining the structure and function of the artery, mechanisms of atherogeneis and its progression, risk factors, the biomarkers associated with atherosclerosis as well as the treatments available. The therapeutic interventions made by drug discovery and nutrition experts aimed at limiting atherosclerosis or attenuating its sequelae would also be discussed.
CONCLUSION
Inflammation participates in all stages of atherosclerosis; all risk factors of atherosclerosis as well as the disease progression have been shown to elicit inflammatory response. Clinical trials, laboratory experiments on animals and tissues in conjunction with population studies have yielded vital clues that lend credence to the claim that atherosclerosis is a chronic inflammatory disease. Atherosclerosis is evidently an inflammatory disease and does not result merely from the build up of lipids: macrophage colony-stimulating factor plays a key role in the regulation of the amounts of macrophages and monocytes and in lesion formation but lipids and other molecules have minimal effect on atherosclerosis development.
Theapeutic measures designed to target the inflammatory mechanisms as well as healthy lifestyles (e.g. good nutrition, exercise) can curb or completely eliminate atherosclerosis. The possibility that members of this class of compounds might also ameliorate hypertensive vascular injury deserves further investigation.
