Atherosclerosis

Arherosclerosis is an inflammatory disease characterized by intense immunological activity. It involves the formation in the arteries of lesions that are characterized by inflammation, lipid accumulation, cell death and fibrosis. Over time, these lesions, which are known as atherosclerotic plaques, mature and gain new characteristics.

The most severe clincial events follow the ruptures of a plaque which exposes the prothrombotic material in the plaqye to the blood and cuaes sudden thrombotic occlusion of the artery at the site of disruption. In the heart, atherosclerosis can lead to myocardial infarction and heart failues, whereas in the arteries that perfuse the brain, it can cause ischaemic stroke and transient ischaemic attacks.

Role of Chemokines: Data obtained using knockout mice show a key role for CC-chemokine ligand 2 (CCL2; also known as MCP1) and its receptor, CC-chemoine receptor-2 (CCR), in the initiation of atheroslerosis. Absence of CCL2 or CCR2 limits the entry of monocytes and T cells into the arterial intima and inhibts atherogenesis.

Macrophages and vascular cells of the forming plaqye also product the T-cell attractants CCL5 (also known as RANTES), CXC-chemoine ligand 10 (CXCL10; also known as IP10) and CXCL11 (also known as ITAC).

Causes

Bacterial infection: P. gingivitis has been assocaited with increased progression of atherosclerosis in rodent model. Invasive P. gingivalis simulates pro-inflammatory cytokines and CAMs in human endothelial cells.

TLR2 plays a critical role in the profession of arteroscleorisis.

Therapies

HSD1 inhibitors: Macrophages in the atherosclerotic lesion express HSDA1. This enzyme appears to amplify the effects of gluccorticoids on atherosclerosis since blockage of HSDA decreases inflammatory tone. HSD1 inhibitors counter regulates inflammatory genes.