Cell migration in cardiovascular diseases

Leukocyte trafficking is a key pathological process during the formation of atheroma. As the acute complications associated with atherosclerosis (heart attack and stroke) are the major causes of morbidity and death worldwide, understanding this process and trying to intervene during atherogenesis is important. Here we have discussed the key molecular process that supports the recruitment of leukocytes to the artery wall, specifically focusing on blood monocytes, and to a lesser extent T-cells and neutrophils. Monocytes and the cells that differentiate from them are found at all stages of disease and are thought to make a major contribution to arterial inflammation. Interestingly, leukocytes can be recruited by blood vascular endothelial cells (BECs) covering the atherosclerotic plaque in the lumen of the artery, even though such a route of entry is prohibited by local hemodynamics and lack of BEC responsiveness to inflammatory mediators in healthy arterial tissues. Moreover, interactions between platelets, BECs, and monocytes appear to support thromboinflammatory pathways of monocyte recruitment which may bypass the regulatory pathways that ordinarily control monocyte trafficking during physiological inflammation. Abnormal routes of leukocyte trafficking appear to support disease initiation and progression in arterial disease and by understanding the molecular mechanisms supporting this we may be able to target pathological leukocyte adhesion, while sparing the normal routes of leukocyte trafficking required for timely and efficient resolution of acute inflammatory responses during infection and tissue injury.