Introduction
Inflammatory cardiovascular disease is used as a term for conditions that affect blood vessels and the heart. The cause of these conditions is the accumulation of fatty deposits in the arteries, known as atherosclerosis. This is known to increase the risk of thrombosis (Thiara., 2015). CVD is one of the main causes of death in the UK and can often be prevented by sensible lifestyle choices (Alexandru et al., 2017). CVD is known to be multifactorial and the exact cause of atherosclerosis remains unclear, but it can be caused by a number of factors such as high cholesterol, diabetes, smoking and obesity (Leong et al., 2017).
CVD can be classified into 4 main types, these are; coronary heart disease (this includes conditions such as angina, heart failure and myocardial infarction), strokes and ischemic attacks, peripheral arterial disease (blockages in the arteries of the limbs) and aortic disease (this includes conditions such as aneurysms that affect the aorta) (Zhang et al., 2017). CVD is a prevalent disease and it is estimated to kill around 17.3 million people worldwide. HeartUK have collected data and statistics show that 160,000 will die from heart and circulatory disease each year and 42,000 people will die prematurely due to CVD (HeartUK., 2018).
The formation of atherosclerotic plaques
The most common cause of CVD is atherosclerosis. It is the build-up of fatty material on the arterial wall. Alone, atherosclerosis is rarely fatal, but the increased risk of thrombosis or plaque rupture is able to cause mortality (Torres et al., 2015). Atherosclerotic lesions are able to form under dysfunctional and activated endothelium. Endothelial cells can disappear, and exposed areas may appear in more advanced lesions. This can be with or without platelets adhering to the subendothelial tissue (Falk., 2006).
This dysfunctional endothelium is responsible for the extravasation of plasma molecules and lipoproteins into the subendothelial space. In the subendothelial space, lipoproteins undergo atherogenic modifications. The mechanisms remain unknown, but it is thought that is mediated by myeloperoxidase, 15-lipoxygenase and nitric oxide synthase (NOS). These lipoproteins will be oxidised and will become proinflammatory, proatherogenic and possess chemotaxic properties (Gistera & Hansson., 2017).
The endothelium will become activated by proinflammatory and atherogenic stimuli. The upregulation of VCAM-1 occurs and leads to the recruitment of monocytes and T lymphocytes. VCAM-1 expression can be seen on the fatty streaks under the epithelium and on mature atheroma. Other adhesion molecules such as P-selectin and E-selectin are also thought to add to the recruitment of inflammatory cells to the atherosclerotic site (Galkina & Ley., 2007).
In the early stages of atherogenesis, monocytes in the blood and T cells are the first cells to respond. In the sites responsible for ischemic events, activated mast cells can be found in the atherosclerotic plaque. Neutrophils are rarely observed in atherosclerosis but can be seen in response to a plaque rupture. Cytokines also play a role in the formation of atherosclerotic plaques. During atherogenesis, oxidised LDLs and CCR2 are known to be upregulated. Monocyte chemotactic protein-1 (MCP-1) is thought to play an important role in the recruitment of inflammatory cells. Macrophages are able to consume the oxidised lipoproteins via scavenger receptors and lead to the formation of foam cells. These foam cells are the hallmark of atherosclerotic lesions. Due to the continuous supply of oxidised lipoproteins, the macrophages will keep consuming the lipoproteins until their demise. In this diseased state, the build-up of cholesterol will not down regulate scavenger receptors like it would with native LDL receptors. A lipid rich core will be formed in the plaque due to the macrophages undergoing apoptosis or necrosis (Chistiakov et al., 2017).
Macrophages can also possess thrombogenic properties by the expression of proteolytic enzymes and tissue factor. The immune cells initially recruited to clear the stimuli are the cause of the plaque formation. The immune cell activation is continuous in atherosclerotic lesions. The promotion of lesion formation in advanced lesions are caused by the upregulation of CD40 and its ligand CD154 (Herbert., 2018). These atherosclerotic lesions can restrict arterial blood flow and cause acute ischemic events. The plaque can also rupture due to the build-up of immune cells and cause haemorrhages (Monaco., 2012).
Introduction to microparticles
Microparticles (MPs) are small vesicles that are heterogenous in size and can range from 0.1?m to 2?m. They are known to originate from the cell membranes of several different cell types such as endothelial cells, leukocytes, platelets and erythrocytes. MPs are biologically active molecules that are usually found in inflammation, coagulation and pathophysiology (Puddu et al., 2010).